Anatomia do sistema oculomotor

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List of Contributors
N.H. Barmack, Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th
Avenue, Beaverton, OR 97006, USA
R.H.I. Blanks, Florida Atlantic University, Charles E. Schmidt College of Science, 777 Glades Road, P.O.
Box 3091, Boca Raton, FL 33431-0991, USA
R. Blumer, Institute of Anatomy, University of Vienna, Waehringerstrase 13, A-1090 Vienna, Austria
U. Büttner, Department of Neurology, Ludwig-Maxmilian University Munich, Klinikum Grosshadern,
Marchioninistr. 15, D-81377 Munich, Germany
J.A. Büttner-Ennever, Institute of Anatomy, Ludwig-Maximilian University of Munich, Petten Koferstr.
11, D-80336 Munich, Germany
P.D.R. Gamlin, Department of Vision Sciences, University of Alabama at Birmingham, 924 South 18th
Street, Birmingham, AL 35294-4390, USA
R.A. Giolli, Department of Anatomy and Neurobiology, University of California, College of Medicine,
Irvine, CA 92697-1275, USA
J.K. Harting, Department of Anatomy, University of Wisconsin Medical School, 1300 University Avenue,
Madison, WI 53706, USA
Y. Hata, Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and
Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
S.M. Highstein, Washington University School of Medicine, Department of Otolaryngology, Box 8115,
4566 Scott Avenue, St. Louis, MO 63110, USA
G.R. Holstein, Department of Neurology and Cell Biology, Mount Sinai School of Medicine, Box 1140,
One Gustave Levy Place, New York, NY 10029, USA
A.K.E. Horn, Institute of Anatomy, Ludwig-Maximilian University of Munich, Pettenkoferstrasse 11,
80336 Munich, Germany
Y. Izawa, Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and
Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
K.Z. Konakci, Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University
Vienna, Waehringerstrasse 13, A-1090 Vienna, Austria
F. Lui, Dipartimento di Scienze Biomediche, Sezione di Fisiologia, Universita di Modena e Reggio Emilia,
Via Campi 287, 41100 Modena, Italy
J.C. Lynch, Department of Anatomy, Ophthalmology and Neurology, University of Mississippi Medical
Center, 2500 N. State Street, Jackson, MS 39216, USA
P.J. May, Department of Anatomy, Ophthalmology and Neurology, University of Mississippi Medical
Center, 2500 North State Street, Jackson, MS 39216, USA
R.A. McCrea, Department of Neurobiology, Pharmacology and Physiology, University of Chicago,
Abbott 09/MC 0926, 947 E. 58th Street, Chicago, IL 60637, USA
M. Möck, Department of Anatomy, Visual Sensorimotor Section, Neurological Clinic, University Hospital
Tubingen, D-72076 Tubingen, Germany
R.M. Müri, Perception and Eye Movement Laboratory, Departments of Neurology and Clinical Research,
University of Bern, Inselspital, CH-310 Bern, Switzerland
v
J.D. Porter, National Institutes of Neurological Disorders and Stroke, 6001 Executive Blvd, NINDS/NSC
2142, Bethesda MD 20892, USA
Y. Shinoda, Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and
Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
yR.F. Spencer, Departments of Anatomy and Otolaryngology, Medical College of Virginia, Richmond,
VA 23298, USA (deceased 2001)
Y. Sugiuchi, Department of Systems Neurophysiology, Graduate School of Medicine, Tokyo Medical and
Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
P. Thier, Department of Cognitive Neurology, Hertie-Institute of Clinical Brain Research, University of
Tubingen, Hoppe-Seyler 3, 72076 Tubingen, Germany
J.-R. Tian, Jules, Stein Eye Institute, 3-310 DSERC, UCLA Medical Center, 100 Stein Plaza, Los Angeles,
CA 90095-7002, USA
B.V. Updyke, Department of Anatomy, University of Wisconsin Medical School, 1300 University Avenue,
Madison, WI 53706, USA
J. Voogd, Erasmus Medical Center Rotterdam, Department of Neuroscience, Box 1738, 3000 DR
Rotterdam, The Netherlands
vi
Preface
This book is dedicated to Bernard Cohen who discovered that the paramedian pontine reticular
formation (PPRF) was essential for the generation of saccadic eye movements 40 years ago. His
work and his unfailing enthusiasm continue to inspire the field of oculomotor and vestibular research.
The updated and extended version of ‘Neuroanatomy of the Oculomotor System’ is a set of reviews which
focus on the functional neuroanatomy and connectivity of the brain areas involved in controlling eye
movements. The first edition of ‘Neuroanatomy of the Oculomotor System’ was published as volume 2 of
‘Reviews in Oculomotor Research’. This series outlived its commercial life and has been discontinued. But
we are delighted to be able to continue the spirit of these reviews in a volume of ‘Progress in Brain
Research’. We chose to publish this updated and extended version as part of this series because it fits well
with the character of ‘Progress in Brain Research’, and because this series is available in most university
libraries. The first chapter is written as an introduction to the oculomotor system: it discusses the different
types of eye movements, the structures involved in their generation and some clinical aspects; it deals with
saccades, the vestibulo-ocular reflex, optokinetic responses, vergence, smooth pursuit and gaze-holding.
Chapter 1 also introduces current concepts such as ‘pulleys’ in the orbit (i.e. the functional consequences of
the Tenon’s capsule), and integrators for gaze-holding. Each of the various topics is picked up in a later
chapter and the neuroanatomy dealt with in more detail. The subsequent chapters are arranged in a
‘bottom –up’ approach; they review the structure and control of eye muscles in the periphery, the next
chapters are on the oculomotor nuclei in the brainstem, then the reticular formation, the vestibular nuclei
and cerebellum. The following chapters move on to more rostral structures, the tectum, the pretectum,
basal ganglia, thalamus and cerebral cortex.
Many new networks influencing eye movements have been discovered, and many new hypotheses have
been proposed, over the 17 years separating the two editions of this book; and as a consequence six new
chapters have been added to the original version. The most provocative of these is Chapter 3, which is a
review of eye muscle proprioceptors and their relationship to the control of eye movements. Here we have
made an attempt to integrate the slightly unpopular field of ‘extraocular proprioception’ into the current
concepts of the oculomotor system, although the evidence for these hypotheses is incomplete. Perhaps it is
too early to come to conclusions on the role of extraocular proprioception, but we have tried to show that
the established facts can be re-interpreted in the light of recent discoveries in fields such as neural
development, genetics and neurotrophins etc., which reveal the factors influencing the development of
muscle spindles, Golgi tendon organs and their neural circuitry. The field of proprioception is fraught with
controversy, and this is reflected in Chapter 3 by the differing views of the authors on the function of a
neural structure unique to eye muscles – the palisade ending. One camp supports the view that they are
motor, the others provide evidence for their sensory nature. Nevertheless, we are convinced that our
differences will be resolved in the future by collaborating with each other; and hence the combined
authorship of Chapter 3.
The other five new chapters in this updated and extended version are devoted to the following topics: the
inferior olive (Chapter 9), which shows how the olivary climbing fibers impose a topography onto the
vii
cerebellum: the pontine nuclei and nucleus reticularis tegmenti pontis (Chapter10), which likewise
determine the organization of cerebellar afferents but of the mossy fiber type: the accessory optic nuclei
(Chapter 13), which provide optokinetic signals to the brainstem, but whose clinical relevance is completely
unknown up to now:and the basal ganglia (Chapter 14), where functional oculomotor networks can now
be followed within the circuitry of the forebrain. Finally, a new review of functional magnetic resonance
imaging (fMRI) studies of oculomotor-related structures has also been introduced (Chapter 16). The eleven
original chapters have been re-written and updated. In almost all cases they have completely altered their
character, depending on whether or not a new scientist, or group of scientists, have taken on the authorship:
this holds for the chapters on the oculomotor nuclei (Chapter 4), reticular formation (Chapter 5), the
vestibular nuclei (Chapter 6), prepositus hypoglossi (Chapter 7), cerebellum (Chapter 8), the superior
colliculus (Chapter 11), pretectum (Chapter 12), cerebral cortex (Chapter 15), and spinal cord (Chapter 17).
In this respect, the old edition is by no means replaced by the new updated version: the chapters of the old
edition will remain useful in their own right because the new authors review different aspects of the
structure. The old Chapter 2 is a masterly review of the properties of eye muscles: Bob Spencer told me in
1987 that he was slow writing it because he had to do a lot of new experiments in order to write it properly.
It has now been thoroughly updated but the authorship of the new Chapter 2 was left in its original
constellation in respect to Robert F. Spencer (1950 – 2001), a great scientist.
The idea of this new and extended version was initiated several years ago by Volker Henn (1943–1997),
who we still sorely miss. Its production has only been possible with the enormous patience and hardwork of
the authors, each of which were chosen for their scientific expertise. I have been very fortunate to have had
the support of Maureen Twaig at Elsevier, as well as the continual encouragement and assistance from
Ahmed Messoudi and Rita Büttner in Munich: I am very grateful to all of them.
Jean A. Büttner-Ennever
Munich, April 2005
viii
Contents
List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
1. Present concepts of oculomotor organization
U. Büttner and J.A. Büttner-Ennever (Munich, Germany) . . . . . . . . . . . . . . . . . . . . 1
2. Biological organization of the extraocular muscles
R.F. Spencer and J.D. Porter (Richmond, VA and Cleveland, OH, USA) . . . . . . . . . 43
3. Sensory control of extraocular muscles
J.A. Büttner-Ennever, K.Z. Konakci and R. Blumer (Munich, Germany and Vienna,
Austria) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
4. The extraocular motor nuclei: organization and functional neuroanatomy
J.A. Büttner-Ennever (Munich, Germany). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
5. The reticular formation
A.K.E. Horn (Munich, Germany) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
6. The Anatomy of the vestibular nuclei
S.H. Highstein and G.R. Holstein (St. Louis, MO and New York, NY, USA) . . . . . . 157
7. Nucleus prepositus
R.A. McCrea and A.K.E. Horn (Chicago, IL, USA and Munich, Germany) . . . . . . . 205
8. Oculomotor cerebellum
J. Voogd and N.H. Barmack (Rotterdam, The Netherlands and Beaverton,
OR, USA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
9. Inferior olive and oculomotor system
N.H. Barmack (Beaverton, OH, USA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
10. The oculomotor role of the pontine nuclei and the nucleus reticularis tegmenti pontis
P. Thier and M. Möck (Tubingen, Germany) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
11. The mammalian superior colliculus: laminar structure and connections
P.J. May (Jackson, MS, USA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
ix
12. The pretectum: connections and oculomotor-related roles
P.D.R. Gamlin (Birmingham, AL, USA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
13. The accessory optic system: basic organization with an update on connectivity,
neurochemistry and function
R.A. Giolli, R.H.I. Blanks and F. Lui (Irvine, CA and Boca Raton, FL, USA and
Modena, Italy) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
14. Oculomotor-related pathways of the basal ganglia
J.K. Harting and B.V. Updyke (Madison, WI, USA) . . . . . . . . . . . . . . . . . . . . . . . . 441
15. Cortico-cortical networks and cortico-subcortical loops for the higher control of eye
movements
J.C. Lynch and J.-R. Tian (Jackson, MS, USA and Los Angeles, CA, USA) . . . . . . . 461
16. MRI and fMRI analysis of oculomotor function
R.M. Müri (Bern, Switzerland) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
17. Long descending motor tract axons and their control of neck and axial muscles
Y. Shinoda, Y. Sugiuchi, Y. Izawa and Y. Hata (Tokyo, Japan). . . . . . . . . . . . . . . . 527
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565
x
Progress in Brain Research, Vol. 151
ISSN 0079-6123
Copyright r 2006 Elsevier B.V. All rights reserved
CHAPTER 2
Biological organization of the extraocular muscles
Robert F. Spencer1 and John D. Porter2,�
1Departments of Anatomy and Otolaryngology, Medical College of Virginia, Richmond, VA 23298, USA
2Departments of Neurology and Neurosciences, Case Western Reserve University and University Hospitals of Cleveland,
Cleveland, OH 44106, USA
Abstract: Extraocular muscle is fundamentally distinct from other skeletal muscles. Here, we review the
biological organization of the extraocular muscles with the intent of understanding this novel muscle group
in the context of oculomotor system function. The specific objectives of this review are threefold. The first
objective is to understand the anatomic arrangement of the extraocular muscles and their compartmental or
layered organization in the context of a new concept of orbital mechanics, the active pulley hypothesis. The
second objective is to present an integrated view of the morphologic, cellular, and molecular differences
between extraocular and the more traditional skeletal muscles. The third objective is to relate recent data
from functional and molecular biology studies to the established extraocular muscle fiber types.
Developmental mechanisms that may be responsible for the divergence of the eye muscles from a skeletal
muscle prototype also are considered. Taken together, a multidisciplinary understanding of extraocular
muscle biology in health and disease provides insights into oculomotor system function and malfunction.
Moreover, because the eye muscles are selectively involved or spared in a variety of neuromuscular diseases,
knowledge of their biology may improve current pathogenic models of and treatments for devastating
systemic diseases.
1. Introduction
The extraocular muscles (EOMs) are the effector
organ for voluntary and reflexive movements of
the eyes. Because the area of high acuity vision, the
fovea, subtends a very small angle of visual space,
the task of gaze control must be accomplished with
high precision through the coordinated activity of
the six EOMs. EOM innervation is by motoneu-
rons in the oculomotor, trochlear, and abducens
nuclei, which represent the final common pathway
upon which signals from a variety of supranuclear
areas converge to produce five distinct classes of
eye movements. The complexity and precision
of eye movements is reflected not only in the
organization of the central oculomotor systems
described elsewhere in this volume, but also in the
very biology of the EOMs. Since skeletalmuscle is
a highly plastic tissue, readily adapting to usage
patterns, one can hypothesize that properties of
the novel EOM phenotype exist to meet a complex
‘‘job description’’ of stabilizing and reorienting eye
position for clear vision. The biological organiza-
tion of EOM is then a consequence of the structure
and function of oculomotor systems and, in turn,
careful analysis of EOM properties can provide
fundamental insights into the status of these neural
control systems in health and disease. The layered
or compartmentalized organization of the EOMs,
into distinctive orbital and global layers, also has
important connotations for the function of this
�National Institutes of Neurological Disorders and Stroke,
6001 Executive Blvd, NINDS/NSC 2142, Bethesda MD 20892.
Tel.: +1 301 496 1917; Fax: +1301 402 1501;
E-mail: porterjo@ninds.nih.gov
DOI: 10.1016/S0079-6123(05)51002-1 43
novel muscle group. In this review, we seek an
understanding of EOM biology in the context of
oculomotor system function.
Knowledge of skeletal muscle biology does not
mean that one understands EOM. As we show
here, many of the ‘‘rules’’ that govern skeletal
muscle biology do not apply to EOM. The EOMs
of some fish exhibit the most remarkable examples
of plasticity found in any skeletal muscle. EOM
precursor cells take alternative developmental paths
to form a weakly electric organ, for navigation, in
the stargazer (Astroscopus sp.) or a heater organ,
that keeps the eye and brain warm during deep
dives, in billfish (Scombroidei order) (Bennett and
Pappas, 1983; Block and Franzini-Armstrong,
1988; Block, 1991). While the EOMs are among
the fastest muscles in mammals, they also possess
slow, non-twitch muscle fibers that are character-
istic of phylogenetically older avian and amphibian
muscles and other traits more typically associated
with cardiac muscle or embryonic skeletal muscle.
It is perhaps because of this paradoxical complex-
ity in their structural organization that a funda-
mental enigma remains in regard to EOM function
in normal eye movements and ocular motility dis-
orders. One objective of this review is to convey an
integrated view of the morphologic, cellular, and
molecular divergence of EOM from prototypical
skeletal muscle.
The multinucleate muscle fiber or myofiber is the
autonomous structural and functional unit of skel-
etal muscle, but all myofibers are not created equal
(Ranvier, 1874). Muscle-to-muscle variability in
function has been ascribed to the relative percent-
age composition of four highly conserved muscle
fiber types (types I, IIA, IIX, and IIB) (Brooke and
Kaiser, 1970; Burke et al., 1971; Peter et al., 1972;
Schiaffino et al., 1989). By contrast, the myofibers
comprising EOM are singularly unique because
they do not respect any of the traditional skeletal
muscle fiber type classification schemes. Several
reviews have described the anatomic organization
of EOM fiber types (Peachey, 1971; Mayr, 1978;
Asmussen, 1979; Chiarandini and Davidowitz,
1979; Spencer and Porter, 1988; Ruff et al., 1989;
Porter and Hauser, 1993a; Porter et al., 1995, 1997;
Porter and Baker, 1996). The emergence of a
consensus EOM fiber type classification scheme
was necessary to interpret later cell and molecular
studies and to subsequently develop an overall
model of EOMmyofiber function. In spite of recent
progress, we only now are beginning to appreciate
the full breadth of adaptations of EOM myofiber
types to their novel role in eye movement control.
A second objective of this review is to integrate
new, multidisciplinary data with established
morphologic profiles to begin to construct an
overall model of the biology of the diverse EOM
fiber types.
Although EOM compartmentalization into the
two distinctive, orbital and global, layers is a long-
recognized and highly conserved feature, its
functional significance has only recently become
clear. Discovery of the EOM pulleys, and the
unique relationship of the muscle layers to the
pulleys and globe, has created a new concept for
the division of labor in EOM (Demer et al., 2000).
A third objective of this review is to relate an-
atomic and molecular properties of the two EOM
layers to this new hypothesis of orbital function.
Here, we address these objectives by building
upon the anatomical framework established in our
prior reviews of EOM (Spencer and Porter, 1988;
Porter et al., 1995, 1997; Porter and Baker, 1996;
Porter, 2002). Knowledge of the compartmental
and myofiber type organization of mammalian
EOM and their relationships to oculomotor system
development, function, and dysfunction represents
an essential framework for future studies.
EOM and orbital gross anatomy
The EOMs exhibit remarkable variation in number,
arrangement (origin and insertion), and innervation
throughout phylogeny. From an early prototype of
four EOMs, a pattern of six ‘‘primitive’’ EOMs has
emerged by an evolutionary process of differentiation
or degeneration. The presence of these six muscles,
the four recti (superior, inferior, medial, and
lateral) and two obliques (superior and inferior),
is rather constant across the vertebrate classes
from cyclostomes to avians, despite variations in
arrangement and innervation (Isomura, 1981). The
last principal EOM, the levator palpebrae superi-
oris, did not make its appearance in phylogeny
44
until mammals. These seven EOMs are relatively
consistent across mammalian species in their gen-
eral location and innervation pattern, although
individual muscle actions show interspecies
variation, particularly apparent in frontal-eyed
(e.g., cat, monkey) versus lateral-eyed (e.g., mouse,
rat, rabbit) animals. These variations are coincident
with species differences in the forward extension of
the maxillary process (Fink, 1953) and the relative
angles of the visual axis and the semicircular canals
(Simpson and Graf, 1981; Ezure and Graf, 1984).
The eye sits within the bony orbit surrounded by
the EOMs, connective tissue, and orbital fat. The
positions of the six rectus and oblique EOMs in cat
and monkey are shown in Fig. 1. Inflections in the
muscle paths due to orbital connective tissue
organization impact EOM actions in primary
and secondary gaze positions (see section ‘‘EOM
pulleys’’). Although the reference visual axes are
parallel and directed straight ahead, the bony
orbits point outward at approximately 231. This
relationship is important to understanding of the
actions of the EOMs because the origin of the
rectus muscles is at the orbital apex and they insert
in a spiral around the ocular limbus in such a
fashion that the superior and the inferior recti
form an angle of 231 with the anterior-posterior
visual axis in the straight-ahead position. The
gross anatomy and general functions of the six
EOMs are reviewed here.
Medial rectus and lateral rectus muscles
The four rectus muscles have a tenon-and-mortise-
like origin from a tendinous ring (annulus of Zinn)
which surrounds the optic foramen and a portion
of the superior orbital fissure (Sevel, 1986). The
medial rectus muscle exhibits a single head of
origin from both the tendinous ring and the dura
that surrounds the optic nerve, and lies medial to
Fig. 1. Drawings illustrating superior and lateral views of monkey and cat orbits, with positions of EOMs and accessory EOMs.
Superior oblique tendon and select other muscles are cut away for clarity of drawings. Note similar localization and insertion of
monkey ALR and cat RBsl. Arrangement of EOMs and accessory EOMs in mouse and rat orbits is similar to that of cat, but the
EOMs are surrounded by the Hardarian gland in rodent. ALR, accessory lateral rectus; IO, inferior oblique; IR, inferior rectus; LR,
lateral rectus, MR, medial rectus, RB, retractor bulbi (sl, il, sm, and im denote superior lateral, inferior lateral, superior medial, and
inferior medial slips, respectively); SO, superior oblique; SR, superior rectus. Drawings by Alex Meredith, PhD.
45
the globe as it courses forward to insert just pos-
terior to thecorneoscleral junction. The lateral re-
ctus, arising from the tendinous ring as two distinct
slips, passes lateral to the globe to insert into the
sclera via a long, broad tendinous expansion. The
innervation of the medial rectus is provided by
the inferior division of the oculomotor nerve, while
the abducens nerve innervates the lateral rectus
muscle. The nerves to both muscles enter proxi-
mally on their global surfaces. Since the insertions
of these muscles are symmetrically distributed
around the horizontal meridian on opposite sides
of the globe, the medial and lateral recti are
functional antagonists that serve as the principal
adductor and abductor of the eye, respectively. No
secondary actions of these muscles are expressed
during movements initiated from the primary
position. Slight vertical and torsional components
induced in extreme positions of gaze are attribut-
able to the actions of the other rectus and oblique
muscles. The arrangements and actions of the
medial and lateral recti are basically identical in
lateral- and frontal-eyed mammals. Expansions of
their tendons of insertion also have attachments
to lacrimal and zygomatic bones (i.e., check
ligaments of Lockwood), which were thought to
serve to restrict extreme movements in the horizontal
plane. More recently, these ‘‘check ligaments’’
have been incorporated into an overall scheme of
orbital connective tissue organization (see section
‘‘EOM pulleys’’) and have been termed entheses
(Kono et al., 2002). The muscle planes of these and
all other EOMs are fixed within the orbit in all
gaze positions (e.g., the horizontal recti do not
sideslip during up and down gaze) (Miller and
Robins, 1987; Miller, 1989).
Superior rectus and inferior rectus muscles
Like the horizontal recti, the vertical (superior and
inferior) recti originate from the tendinous ring at
the apex of the orbit and course forward to insert
anterior to the equator of the globe. The superior
rectus, like the medial rectus, muscle has an addi-
tional origin from the dura of the optic nerve
(Sevel, 1986). The nerves to the superior and
inferior recti, the superior and inferior divisions of
the oculomotor nerve respectively, enter the global
surface of the proximal portion of each muscle.
Although elevation and depression of the globe are
the primary actions of the vertical recti, their
origins lie medial to the globe such that they exhibit
secondary roles in the horizontal and torsional
planes. With the eyes in the primary position, the
primate vertical recti intersect the globe at an angle
of 231 lateral to the visual axis. Thus the superior
rectus has a secondary role in adduction and
intorsion, while the inferior rectus assists in ad-
duction and extortion. Though the primary actions
of the vertical recti are the same in lateral-eyed
mammals, the angle of force of these muscles shifts
201 medial to the visual axis thereby altering their
secondary actions. As a result, in lateral-eyed
mammals the superior rectus secondarily extorts
and abducts, while the inferior rectus has a supple-
mental role in intorsion and abduction. A modified
distal segment of the superior rectus, the lateral
arm, is evident in rabbit and is primarily com-
prised of orbital layer multiply innervated muscle
fiber types (Briggs et al., 1988) (see section
‘‘Detailed organization of EOM fiber types’’). A
similar structure may exist in humans (Kono et al.,
2002). Unlike the horizontal recti, the superior and
inferior recti do not have the enthesis connections
to the orbital walls (Kono et al., 2002).
Superior oblique muscle
The superior oblique muscle, like the four recti,
arises from the tendinous annulus at the apex of the
orbit. A small fascicle of muscle fibers on the medial
surface of the muscle originates from the medial
bony wall of the orbit. Coursing forward from an
origin which lies dorsomedial to that of the medial
rectus, the superior oblique passes through a fib-
rocartilaginous ring, the trochlea, and turns laterally
to insert on the superior aspect of the globe. The
insertion of this muscle falls posterolateral to the
central point of the globe in frontal-eyed mammals,
but anterolateral in lateral-eyed mammals. The
trochlear nerve, upon entering the superior orbital
fissure, courses medially to enter the superior
portion of the orbital surface of the muscle. From
the primary position, the predominant action of
46
this muscle in both lateral- and frontal-eyed
animals is intorsion. Differences in the point of
insertion of the superior oblique in the primate
versus the rabbit lead to clear differences in its
secondary actions. The primate superior oblique
secondarily depresses and abducts the globe, while
that of the rabbit secondarily elevates and adducts.
An anomalous muscle, the gracillimus orbitis (of
Bochdalek) or comes obliqui superioris (of Albin),
when present, originates from the proximal dorsal
surface of the superior oblique muscle, inserts on
the trochlea and/or its surrounding connective
tissue, and is innervated by a branch of the fourth
nerve (Whitnall, 1921).
Inferior oblique muscle
In contrast to the origin of the other principal
EOMs from the annulus of Zinn, the inferior
oblique muscle arises from the maxillary bone in
the medial wall of the orbit. The origin of the
inferior oblique muscle furthermore may display
considerable variation in its anatomical relation-
ship to the nasolacrimal canal (Whitnall, 1921).
The muscle passes ventral to the tendon of the
inferior rectus and inserts on the lateral aspect of
the globe medial to the tendon of the lateral rectus.
The insertion of the inferior oblique, like that of
the superior oblique, is posterior to the equator in
the primate and anterior to the equator in the
rabbit, thereby resulting in the same primary ac-
tion, extorsion, but different secondary actions.
The inferior oblique of lateral-eyed animals second-
arily depresses and adducts, while that of frontal-
eyed animals elevates and abducts. Innervation is
provided by a branch of the inferior division of the
oculomotor nerve that enters the muscle near its
posterior border.
Levator palpebrae superioris muscle
The levator palpebrae superioris has a narrow
origin from the orbital surface of the lesser wing of
the sphenoid bone, just above the optic foramen
and the origin of the superior rectus. In its distal
course, this muscle crosses the superior aspect of the
globe and fans out to insert via broad aponeuroses
onto both the skin of the upper eyelid and the
superior tarsal plate. Since a scleral insertion is ab-
sent, this muscle exerts no direct influence upon the
globe, although an indirect influence is mediated by
a partial blending of the levator aponeurosis with
the tendon of the superior rectus muscle. Innerva-
tion is provided by a branch of the superior division
of the oculomotor nerve that passes to the proximal
portion of the muscle either through or lateral to
the superior rectus. The levator palpebrae functions
in elevation of the upper eyelid. Occasionally,
though perhaps not infrequently, two anomalous
muscles are associated with the levator palpebrae,
and, like the latter, are innervated by branches from
the superior division of the 3rd nerve (Whitnall,
1921; Isomura, 1977; Sacks, 1985). The tensor
trochleae (of Budge) arises from the medial border
of the levator muscle and inserts onto the trochlea
of the superior oblique muscle and/or its surround-
ing connective tissue. A muscle of similar name and
insertion, but originating from the ventral rim of the
optic foramen in proximity to the origin of the su-
perior rectus muscle and innervated by the fourth
nerve, has been described in the rabbit (Murphy
et al., 1986). The transversus orbitus attaches
between the medial and lateral walls of the orbit
connecting with the levator muscle en route.
Accessory EOMs
In addition to the seven principal EOMs, many
vertebrates possess accessory EOMs. Accessory
EOMs in cat and monkey are shown in Fig. 1. In
most species, the accessory muscle takesthe form
of the retractor bulbi (Hopkins, 1916; Cords, 1924;
Isomura, 1981). The retractor bulbi is correlated
with the presence of a nictitating membrane, and
these structures are synergistic in reflex retraction
of the globe in response to corneal stimulation.
The retractor bulbi first appears in phylogeny as a
continuous sheath that surrounds, or two slips
lying dorsal and ventral to, the optic nerve in
amphibians. In both amphibians and reptiles, the
retractor bulbi is paired with the membranae nic-
titans muscle. In avians, these two muscles are re-
placed by quadratus membranae nictitans and
pyramidalis muscles. The mammalian retractor
47
bulbi muscle variably has two (mouse), three
(dog), or four (rat, rabbit, cat) slips. Innervation
of the retractor bulbi exhibits species-specific
patterns from branches of the oculomotor and/or
abducens nerves (Spencer and Sterling, 1977;
Grant et al., 1979, 1981; Crandall et al., 1981;
Meredith et al., 1981; Evinger et al., 1987). With
the regression of the nictitating membrane to a
vestigial plica semilunaris in primates, the retrac-
tor bulbi is reduced to a single homologous slip in
the monkey, the accessory lateral rectus muscle,
which is innervated by the abducens nerve (Spencer
and Porter, 1981; Schnyder, 1984). An accessory
lateral rectus muscle may render monkeys resistant
to esotropia (Boothe et al., 1990) and has been re-
ported in humans only in one case of congenital
oculomotor nerve palsy (Park and Oh, 2003).
EOM pulleys
The recent discovery of EOM pulleys, and their
interrelationship with the compartmentalized struc-
ture of the EOMs (see section ‘‘Compartmental
organization of EOM’’), represents a paradigm
shift in oculomotor function. Evidence that rectus
muscle bellies remain relatively fixed in the orbit
despite surgical transposition of their insertions
provided the first suggestion that EOM muscle
paths were fixed relative to the orbit (Miller et al.,
1993). Subsequent anatomical and imaging studies
characterized fibroelastic sleeves, or pulleys, repre-
senting specializations in Tenon’s capsule (Fig. 2).
EOM pulleys are located approximately at the
equator of the globe and suspended from the bony
orbit by collagen/elastin/smooth muscle struts or
entheses (Demer et al., 1995; Porter et al., 1996;
Clark et al., 1997; Kono et al., 2002). Adjacent
muscle pulleys are intercoupled by connective
tissue bands. The pulleys provide inflection points
in EOM paths, thereby serving as functional or-
igins for each muscle. Species differences in pulley
morphology correlate with known differences in
EOM biology and visuomotor function in rat ver-
sus humans (Khanna and Porter, 2001). The recent
finding that the two distinct EOM compartments
or layers have separate insertion points led to
formulation of the active pulley hypothesis, in
which movements of pulley (by the orbital layer)
and globe (by the global layer) are coordinated but
not necessarily coincident (Demer et al., 2000). The
active pulley system uses orbital layer motor units
to alter pulley positions and thereby adjust EOM
vector forces in different gaze positions, greatly
simplifying the task of central oculomotor control
systems by making commands independent of in-
itial eye position (Clark et al., 2000). Any role that
the smooth muscle tissues, and their specialized in-
nervation (Demer et al., 1997), might play in pulley
positional control is poorly understood at this time.
The functional context of the EOMs
An understanding of the novel biology of the
EOMs is incomplete without an appreciation for
the demands of ocular motility (for a thorough
review, see other chapters of this volume and Leigh
and Zee, 1999). The reflexive oculomotor control
systems that stabilize images on the retina, thereby
preventing blur during head/body movement, are
the phylogenetically oldest and form a base upon
which the other eye movement systems operate.
Thus, the vestibulo-ocular and optokinetic reflexes
are found in all vertebrates, but visual targeting
movements, such as saccades and smooth pursuit,
appear later in phylogeny and vergence move-
ments are associated only with the evolution of
frontally placed eyes and high acuity specializa-
tions of the retina (e.g., area centralis, fovea).
Elaboration of the more sophisticated oculomotor
control systems correlates with specific, patterned
changes in EOM biology (see section ‘‘Differences
in EOM fiber types in the same and different
species’’). Accessory EOMs are typically restricted
to species with incomplete bony orbits, where re-
flex retraction is required to protect the eye.
While the oculomotor system is arguably the
best understood of skeletomotor control systems,
it also is among the most complex. Unlike most
skeletal muscles, which often are tightly role-specific,
individual EOMs serve very diverse functional
repertoires and execute eye movements almost
continuously throughout waking hours. Binocular
alignment and maintenance of steady fixation upon
targets are essential for clear vision and must be
48
accomplished within very fine tolerances or else blur
and diplopia (double vision) result. On one hand,
EOM responds to polymodal sensory signals to
produce slow, smooth changes in eye position in
vestibulo-ocular, optokinetic, vergence, and pursuit
movements that stabilize and/or track visual targets.
On the other hand, in acquiring novel visual targets
the EOMs must execute saccadic eye movements
that can exceed 6001/s.
Skeletal muscle characteristics are directly influ-
enced by the patterned activity of the motoneurons
that innervate them (Pette, 2002). Oculomotor
motoneurons represent the common output of the
control systems described above and have highly
stereotyped discharge patterns (Robinson, 1970),
including: (a) tight linkage between sustained
activity and eye position, (b) rapid and large puls-
es of motoneuron discharge associated with sac-
cadic eye movements, and (c) an overall high level
of motoneuron activity, exceeding that of spinal
motoneurons by an order of magnitude. EOM
fibers then must be responsive over an unprece-
dented dynamic range that requires adaptations for
contraction speed and fatigue resistance well be-
yond that experienced by the more typical skeletal
muscles. To this end, EOM utilizes the full range
of phenotypic options available to adult skeletal
muscle plus traits strategically borrowed from
Fig. 2. Diagrammatic representation of orbital connective tissue relationships to the EOMs and eye, including the specializations of
Tenon’s capsule, the rectus muscle pulleys. The connective tissues of the orbit are thickened to form pulleys for the four rectus muscles
and inferior oblique. Interconnections between, and anterior and posterior to, the pulleys are the pulley sling. Differential distribution
of orbital smooth muscle, collagen, and elastin components of pulleys and associated tissues is indicated. The three coronal views are
represented at the levels indicated by arrows in the horizontal section. Separate insertions of orbital and global layers upon pulley and
globe, respectively, also are indicated. IO, inferior oblique; IR, inferior rectus; LPS, levator palpebral superioris; LR, lateral rectus;
MR, medial rectus; SO, superior oblique; SR, superior rectus (figure courtesy of J.L. Demer and J.M. Miller; see Demer, 2000).
49
phylogenetically primitive skeletal muscle, imma-
ture skeletal muscle, and cardiac muscle. There
likely is a causal relationship between the wide
dynamic range of oculomotor control systems and
the complexity and diversity of EOM.
Compartmental organization of EOM
Skeletal muscles are generally heterogeneous in
cross-sectional appearance and compartmentalized
or layered patterns may be evident. Various func-
tional advantages of compartmentalization in tra-
ditional skeletal muscles have been previously
addressed (English and Letbetter, 1982; Eason
et al., 2000). Likewise, the rectus and oblique EOMs
are characterized by a distinctive compartmentali-zed organization (Kato, 1938) (Fig. 3A). Each has
an outer orbital layer adjacent to the periorbita and
orbital bone and an inner global layer close to the
optic nerve and eye. In some species, a transitional
zone (e.g., monkey), containing an admixture of
muscle fiber types from either layer, or a connec-
tive tissue band (e.g., rabbit) may be evident between
the orbital and global layers. A thin muscle fiber
layer external to the orbital layer, termed the mar-
ginal zone (Wasicky et al., 2000) or peripheral
patch layer (Harker, 1972), has been documented
in some species. In the rectus muscles, the orbital
layer is comprised of smaller diameter fibers and
typically is c-shaped, encompassing the global
layer except for a gap left adjacent to the optic
nerve or globe. In the oblique muscles, the orbital
layer often completely encircles the global layer.
The global layer extends the full muscle length,
inserting into the sclera via a well-defined tendon,
while the orbital layer ends before the muscle be-
comes tendinous. Recent studies have shown that
this early termination of the orbital layer is a con-
sequence of its insertion into the muscle pulley, at
approximately the equator of the globe (Demer
et al., 2000) (Fig. 2). By contrast, neither the le-
vator palpebrae superioris nor the accessory
EOMs have an orbital layer compartment, a find-
ing that correlates with their lack of muscle pulleys.
In addition to the clear differences in myofiber
diameter, the two EOM layers are distinguished by
substantial morphologic and immunocytochemical
differences. First, the interrelated features of
mitochondrial content, oxidative enzyme activities
(e.g., SDH, NADH-TR), and microvascular net-
work all are more developed in the orbital layer.
Collectively, these traits correlate with the high
fatigue resistance and continuous activation of the
orbital layer. Second, the orbital layer expresses
traits usually associated with developing skeletal
muscle. While traditional skeletal myofibers exhibit
a developmental transition in expression of embry-
onic to neonatal to adult myosin heavy chain iso-
forms, adult orbital layer myofibers retain the
embryonic myosin heavy chain (Myh3) (Wieczorek
et al., 1985; Jacoby et al., 1990; Brueckner et al.,
1996). Neural cell adhesion molecule (NCAM), a
cell surface molecule normally downregulated dur-
ing myogenesis, also persists on virtually all orbital,
but only some global, layer fibers (McLoon and
Wirtschafter, 1996). A similar pattern is apparent
Fig. 3. Histological profiles of the EOM layers (A) and fiber
types (B, C) in the monkey lateral rectus muscle. Note general
fiber type size differences, with the c-shaped orbital layer con-
taining smaller diameter fibers. Profiles of the SIFs (1, 3–5) and
MIFs (2, 6) in the orbital (B) and global (C) layers are indi-
cated. Phase contrast light photomicrographs of semithin
(1mm) sections highlight differences in mitochondrial content
of different muscle fiber types. 1, orbital SIF; 2, orbital MIF; 3,
global red SIF; 4, global intermediate SIF; 5, global white SIF;
6, global MIF.
50
for the embryonic (g) acetylcholine receptor (AChR)
subunit, as it is present at all neuromuscular junc-
tions of orbital layer myofibers, but only at those of
some global layer myofibers (Kaminski et al., 1996).
Because few investigators work on the cell and
molecular biology of EOM, observations such as
the orbital layer retention of embryonic traits are
sparse. To more efficiently identify such orbital and
global layer specializations, we used laser capture
microdissection to isolate EOM layer-specific sam-
ples and then determined their gene expression sig-
natures by high-throughput DNA microarray
analyses. Differential expression profiling identified
181 transcripts with preferential expression in the
orbital or global layer, encompassing genes with a
wide range of functions (see Khanna et al., 2004 and
accession number GSE 907 in the National Center
for Biotechnology Information (NCBI) Gene Ex-
pression Ontology (GEO) database). Among these,
several slow/cardiac muscle markers were preferen-
tially expressed in the orbital layer (TNNC1,
MYH7, MYH6, CSRP3, TNNT2, FHL1, NRXN3,
andNEBL). These data suggest that the orbital may
be functionally slower than the global layer and that
properties of orbital layer fibers alone may explain
and extend several prior findings of cardiac muscle-
specific gene or protein expression in EOM.
Overall, the orbital and global layers are very
different in their morphologic and gene expression
profiles, consistent with their respective muscle pul-
ley and eye movement roles. Preferential expression
of the transcription factor, CSRP3 (and transcripts
that are regulated by CSRP3; e.g., FHL1, MYH3)
(Khanna et al., 2004), by the orbital layer is a par-
ticularly interesting finding. CSRP3 responds to
muscle stretch by activating transcripts associated
with early myogenesis (Knoll et al., 2002). Orbital
layer expression of CSRP3 may mechanistically
link the continuous activity of this layer against
elastic elements of muscle pulleys to the orbital
layer retention of various embryonic traits.
Traditional skeletal muscle fiber types
Most skeletal muscles are comprised of variable
percentages of four conserved muscle fiber types.
The myofiber traits that are responsible for
contraction speed and fatigue resistance are not
independently regulated. Instead, myofiber prop-
erties that determine speed and fatigability are
co-expressed in specific patterns that led to the
recognition of discrete muscle fiber types. The
major myofiber classification schemes (Brooke
and Kaiser, 1970; Peter et al., 1972; Burke et al.,
1973; Gauthier and Lowey, 1979; Schiaffino et al.,
1989) agree on three to four fiber types in typical
skeletal muscle: (a) slow-twitch, fatigue resistant
(red or type I), (b) fast-twitch, fatigue resistant
(intermediate or type IIA), (c) fast-twitch, inter-
mediate (type IIX), and (d) fast-twitch, fatigable
(white or type IIB). Structural and functional
properties of these four traditional fiber types are
summarized in Table 1. Muscle fiber types have
distinct functional identities (Close, 1972; Burke
et al., 1974), each with a relatively narrow optimal
working range such that their collective actions
are required to achieve typical physiologic whole
muscle force-velocity profiles. These four fiber
types are found in various proportions in virtually
every mammalian skeletal muscle. For example,
slow fatigue-resistant muscles like soleus are prin-
cipally comprised of types I and IIA, while type
IIB fibers predominate in fast, fatigable muscles
like gastrocnemius. It is well recognized that the
four discrete myofiber types may represent pheno-
types along a continuum in variation of myofiber
traits. Nonetheless, the fiber type classification
schemes have been an essential means of under-
standing muscle function and are of considerable
value in diagnosis and muscle disease modeling, as
several neuromuscular diseases preferentially in-
volve specific muscle fiber types.
Initial gene expression profiling studies have sug-
gested that differences between muscles that are
comprised of predominately type I versus type IIB
myofibers are relatively modest (Campbell et al.,
2001). However, more recent data support a greater
degree of divergence among skeletal muscle groups
than can be explained simply by differences in com-
position of stereotypic fiber types (Porter et al.,
2004). These data suggest that there might be more
variability among the traditional muscle groups and
myofiber types than is currently known.
Despite the value of the fiber type concept for
over 130 years (Ranvier, 1874), myofibers present
in some muscle groups do not appear to respect
51
traditional classification schemes. The allotype
concept originated as a framework to account
for the phenotypic range available to skeletal mus-
cle (Hoh et al., 1988, 1989). Three allotypes were
defined on the basis of their potential toexpress
specialized myosins: masticatory (super fast myo-
sin), EOM (EOM-specific myosin, designated
Myh13), and limb (no allotype-specific myosins),
and their appearance is dependent upon an inter-
action of muscle lineage with appropriate inner-
vation patterns. The distinctive fiber types
comprising the EOM allotype are discussed here.
Overview of EOM fiber types
Early morphologic and physiologic studies recog-
nized that myofibers present in mammalian EOM
were atypical. Siebeck and Kruger (1955) identified
two basic EOM fiber types, one type similar to the
typical twitch fibers of mammalian skeletal muscles
(now designated singly innervated fibers or SIFs)
and the other similar to slow fibers atypical for
mammalian skeletal muscle (now designated mul-
tiply innervated fibers or MIFs). The SIFs of rectus
and oblique EOMs are invariably fast-twitch
Table 1. Structural and functional profiles of the routine skeletal muscle fiber types
Terminologiesa
Brooke and Kaiser (1970) I IIA IIX IIB
Peter et al. (1972) Slow-twitch-oxidative Fast-twitch-oxidative
glycolytic
Fast-twitch-glycolytic
Burke et al. (1973) S FR F (int.) FF
Gauthier and Lowey (1979) Red (slow) oxidative Red (fast) oxidative
glycolytic
Intermediate White glycolytic
Schiaffino et al. (1989) I IIA IIX IIB
Histochemical profiles
Myosin ATPase (pH 9.4) Low High High High
Myosin ATPase (pH 4.6) High Low Intermediate Intermediate
Myosin ATPase (pH 4.3) High Low Intermediate Low
SDH (mitochondrial aerobic) High Intermediate–high Intermediate Low
NADH-TR (aerobic) High Intermediate–high Intermediate Low
LDH (anaerobic) High Intermediate–high Intermediate Low
Men-a-GPD (anaerobic) Low High Intermediate High
PAS (glycogen) Low High Intermediate Intermediate–high
Phosphorylase Low High High High
Oil Red O (lipid) High Low Low Low
Alkaline phosphatase
(capillaries)
High High Low Low
Immunocytochemical profiles
Myosin heavy chain Myh7 (I/b-cardiac) Myh2 (IIA) Myh1 (IIX) Myh4 (IIB)
Ultrastructural profilesb
Z-line Wide Wide Narrow Narrow
Mitochondria Many, small Many, large Moderate, small Few, small
Sarcoplasmic reticulum, T-
tubules
Elaborate, narrow Elaborate, narrow Moderate, small Compact, broad,
parallel
Neuromuscular junctions Large, widely spaced,
deep folds
Discrete, separate,
small, elliptical, shallow,
sparse folds
Long and flat; long,
branching, closely
spaced folds
Physiological profilesc
Twitch contraction time (ms) Slow Intermediate Fast Fast
Twitch tension (g) Very low Low Intermediate High
Relative fatigue resistance Resistant (very) Resistant (moderate) Intermediate Sensitive
aTerminology from the major skeletal muscle fiber type classification schemes. bConsenus morphologic traits from multiple studies
(Gauthier, 1969; Padykula and Gauthier, 1970; Schiaffino et al., 1970). cConsensus physiological traits derived from multiple studies
(Close, 1972; Burke et al., 1973, 1974).
52
(among EOMs, slow-twitch fibers are found only in
the levator palpebrae superioris; see Porter et al.,
1989). MIFs have been found in EOM and a few
other, highly specialized craniofacial muscles (e.g.,
tensor tympani and laryngeal muscles) (Fernand
and Hess, 1969; Mascarello et al., 1982; Veggetti
et al., 1982; Han et al., 1999). We suggest that
MIFs, while exceptionally rare in skeletal muscle,
may be more prevalent among craniofacial muscles
than is currently appreciated. Physiologic studies
identified two MIF types in EOM, differing on the
basis of location within the orbital or global layers
and their physiological ability to propagate action
potentials (Hess and Pilar, 1963; Bach-y-Rita and
Ito, 1966; Pilar and Hess, 1966; Pilar, 1967). The
two types of EOM MIFs resemble the multiply
innervated fibers that are found in amphibian
(similar to global layer MIFs) and avian (similar to
orbital layer MIFs) skeletal muscles (Morgan and
Proske, 1984). Interestingly, the neuromuscular
junctions associated with SIFs and MIFs appear to
exhibit very similar molecular organization and
both have only modest differences from those of
other skeletal muscles (Khanna et al., 2003b).
Since these early studies, EOM fiber typing has
evolved such that there now is a consensus on a six
fiber type classification scheme for mammalian
EOM (for a historical review, see Spencer and
Porter, 1988). There are also several extensive
reviews of this fiber classification scheme (Spencer
and Porter, 1988; Porter et al., 1995; Porter and
Baker, 1996). While any single measure (e.g., myo-
fibrillar ATPase) might lead one to believe that
EOM is comprised of traditional skeletal muscle
fiber types, broader morphologic/histochemical/
immunocytochemical profiles show that the estab-
lished skeletal muscle classification schemes simply
do not apply to EOM. A reasonable assumption is
that the relatively large number of EOM fiber types,
six versus the three to four of typical skeletal muscle,
reflects the complexity and variety of eye movements.
EOM fiber types have been extensively charac-
terized in monkeys, rabbits, rats, and mice and
there is evidence that human EOMs contain sim-
ilar fiber types (Wasicky et al., 2000). Recent
studies, relying upon myosin heavy chain expres-
sion patterns alone, have suggested that EOM
may be more complex in fiber type content than
the six fiber type scheme (McLoon et al., 1999;
Kjellgren et al., 2003a, b). Myosin heavy chain is a
key determinant of contractile properties; multi-
ple myosin genes encode proteins differing in
contraction speed and energetic demands such
that an individual skeletal muscle fiber typically
expresses the one myosin isoform that is best
suited for its workload. EOM is unique in its
broad utilization of options from the myosin
heavy chain family and its frequent heterogeneity
in myosin expression within single myofibers.
Specifically, EOM expresses virtually all known
striated muscle isoforms of myosin heavy chain,
including traditional adult skeletal (Myh1 or type
IIX, Myh2 or IIA, Myh4 or IIB, and Myh7 or I/b-
cardiac), developing skeletal (Myh3 or embryonic
and Myh8 or perinatal), cardiac-specific (Myh6 or
a-cardiac), and a tissue-specific (Myh13 or EOM-
specific) isoform (Bormioli et al., 1979; Wieczorek
et al., 1985; Jacoby et al., 1990; Asmussen et al.,
1993; Rushbrook et al., 1994; Brueckner et al.,
1996; Jung et al., 1998; Winters et al., 1998;
McLoon et al., 1999; Pedrosa-Domellöf et al.,
2000; Rubinstein and Hoh, 2000; Wasicky et al.,
2000; Briggs and Schachat, 2000, 2002; Schachat
and Briggs, 2002). If we are to obtain an overall
understanding of the properties of EOM fiber
types, it is essential to relate myosin expression
patterns, identified by immuncytochemistry and/or
in situ hybridization, to the range of other myo-
fiber traits. Incorporation of much of the recent
myosin expression data into the existing EOM
myofiber classification scheme, however, is prob-
lematic. Possible species differences in myosin
expression patterns, heterogeneity in the batteries
of myosin antibodies used, failure to consider factors
such as the longitudinal variations in the same fiber,
and the frequent failure to use a fiber type identifying
marker (e.g., trichrome stain) in adjacent sections
serve to complicate any synthesis of myofiber traits.
As noted above, it can be misleading to base
fiber classification schemes upon any single trait,
as this may identify mere variations in the same
fiber types. Although four SIF types are described
in mammalian EOM, every fiber cannot be fit to
the absolute criteria of a single type. The aggregate
population of EOM SIFs, therefore, may form a
continuum of fast-twitch fibers that differ in
53
contraction speed and fatigability (Nelson et al.,
1986), not unlike the situation for the three fast-
twitch fiber types in traditional skeletal muscles. If
fiber typing is to provide a useful tool for under-
standing EOM biology, we argue that further
additions to the myofiber classification schemes
must allow for such variability and base anynew
types upon the identification of conserved patterns
across a broad range of myofiber traits.
The six established EOM fiber types are desig-
nated according to their layer distribution (orbital
or global), innervation type (singly or multiply),
and mitochondrial content (red, intermediate, or
white). All EOM SIFs have profiles consistent with
fast-twitch function, but atypical for skeletal mus-
cle fast-twitch fibers, contain very little glycogen.
Fiber type traits are summarized in Table 2 and in
the following section. Fiber type repertoires of the
levator palpebrae superioris, retractor bulbi, and
accessory lateral rectus muscles differ from the
scheme presented here and are discussed elsewhere
(Alvarado et al., 1967; Pachter et al., 1976; Spencer
and Porter, 1981; Gueritaud et al., 1986; Porter
et al., 1989). It is important to note that fiber types
of the retractor bulbi are more like those of limb
musculature; this may have direct disease conse-
quences, since the retractor does not exhibit the
sparing in muscular dystrophy that is seen for EOM
(Ragusa et al., 1996; Porter and Karathanasis,
1998; Porter et al., 2001b, 2003b).
Detailed organization of EOM fiber types
Here, we present a composite view of each of the
six recognized EOM myofiber types. Two of these
fiber types localize to the orbital layer (one SIF
and one MIF) and four localize to the global layer
(three SIFs and one MIF). A characteristic feature
of EOM is the overall small myofiber diameter
relative to most other skeletal muscles. The EOM
fiber types are largely conserved across species;
known species differences are addressed in a sub-
sequent section. Morphologic descriptions are
based upon rhesus monkey EOM, while histo-
chemical and immunocytochemical data are com-
piled from a variety of species. The myosin
expression patterns indicated here are only those
isoforms that can be clearly linked to specific fiber
types; thus, these likely are incomplete represen-
tations of the actual expression patterns.
The orbital singly innervated fiber type
Orbital SIFs (Figs. 3B and 4A, and Table 2)
represent the predominant fiber type (80%) in the
orbital layer of rectus and oblique muscles. The or-
bital SIFs contain small myofibrils, surrounded by
abundant sarcoplasmic reticulum, and high
mitochondrial content (Fig. 5A). At mid-belly, or-
bital SIF diameter is largest and the fibers taper
proximally and distally. Mitochondria form char-
acteristically large central and subsarcolemmal clus-
ters. Since mitochondria comprise a rather large
volume of the orbital SIFs (20% by volume), myo-
fibril volume is exceptionally low (60%) in compar-
ison to the range seen in most skeletal muscles
(70–85%) (Hoppeler and Fluck, 2002). This is con-
sistent with the general EOM trait of low force de-
velopment. The histochemical profile of orbital SIFs
suggests that they are fast-twitch and fatigue resist-
ant, but also have capacity for anaerobic metabo-
lism. Orbital SIFs contain unusually high lipid
content. A single neuromuscular junction is present
at approximately the middle of each fiber, usually
encircling the fiber; nerve terminals are embedded in
deep depressions of the sarcolemma and exhibit few,
irregular postsynaptic folds (Fig. 6A).
Myosin expression in orbital SIFs is heterogene-
ous, with expression of a unique myosin gene only
seen in EOM and laryngeal muscles (Myh13) and a
developmental myosin isoform (Myh3) (Wieczorek
et al., 1985; Jacoby et al., 1990; Brueckner et al.,
1996). This myosin expression pattern raises two
critical issues: (a) phylogenetic analysis of Myh13
indicates that it diverged early from an ancestral
myosin and has substantial structural differences
from other fast isoforms (Briggs and Schachat, 2000;
Shrager et al., 2000) and (b) retention of develop-
mental myosin isoforms in adult skeletal muscle is
rare. Myosin isoforms are specialized to provide
specific contractile force/velocity at a specific energy
cost. The unique myosin expression profile of orbital
SIFs is suggestive of a highly specialized role in eye
movements. Lucas and Hoh (2003) have suggested
54
Table 2. Ultrastructural and histochemical profiles of extraocular muscle fiber types
Orbital Global
Fiber type: 1 2 3 4 5 6
Ultrastructural profiles
Myofibrils
Extent Small Large Small Small Small Large
Size (mm)
Rata 0.24 0.20–0.81 0.26 0.34 0.41 0.61
Monkeyb 0.30 0.36–0.58 0.27 0.41 0.51 0.67
Separation Well delineated Moderately delineated Well delineated Well delineated Well delineated Poorly delineated
Volume fractionc (%) 60 78 55 65 71 83
Sarcoplasmic recticulum
Extent Moderately developed Modestly developed Moderately developed Well developed Well developed Poorly developed
Location Predominantly I band I band Predominantly I band Predominantly I band I4A band I band
Volume fraction (%)
Ratc 9 6 10 14 16 4
Monkeyb 7.7–17.4 7.0–16.2 9.2 18.3 19.5 4.8
T-tubules
Extent Well developed Poorly developed Well developed Well developed Well developed Poorly developed
Location A/I junction Irregular A/I junction A/I junction A/I junction Irregular
Mitochondria
Number Very many Few–many Many Many Few Few
Extent Large Small Large Moderate Small Small
Size (mm)
Monkeyb 0.13–0.28 0.07–0.14 0.22 0.19 0.20 0.06
Disposition Aggregated Single Aggregated Single Single Single
Volume fraction (%)
Ratc 20 6 24 13 5 5
Monkeyb 18.1–27.3 7.9–20.6 22.3 13.8 6.8 6.8
Z-line
Extent Intermediate Wide Intermediate Narrow Narrow Wide
Width (mm)
Ratc 73 118 76 54 48 100
Histochemical profilesd
Trichrome Coarse/granular Granular/fine Coarse/granular Granular Granular/fine Fine
Mean diameter (mm) 24.873.8 19.373.2 27.274.7 34.574.6 46.776.2 35.774.1
Percentage (%) 80 20 33 25 32 10
Myosin ATPase 9.4 +++ +++ +++ +++ +++ +/–
Myosin ATPase 4.6 +/- +++ +/- +/– +/– ++++
SDH +++/++++ ++ ++++ +++ ++ +
NADH-TR +++ ++ ++++ +++ ++ +
LDH ++/+++ ++ ++++ +++ ++ +
Men-a-GPD ++/+++ + ++ +++ ++++ +
5
5
Table 2 (continued )
Orbital Global
Fiber type: 1 2 3 4 5 6
Sudan black ++/+++ + +++ ++ ++ +
PAS ++/+++ +/– ++ + + +/–
Phosphorylase ++/+++ + +++ + + +
Oil RedO ++/+++ + +++ ++ + +
Alkaline phosphatase ++++ ++ +++ ++ + +
AChE Focal, encircle Multiple Focal Focal Focal Multiple
Physiological profiles
Contraction speed Fast Twitch/tonic Fast Fast Fast Tonic
Fatigue resistance High Intermediate High Intermediate Low Low
aQuantitative data from Pachter (1983) in rat superior oblique muscle. Ranges for the orbital MIF (2) indicate proximo-distal variations within single fibers examined in
serial sections. bQuantitative data from Pachter (1982) in monkey superior rectus muscle. Ranges for the orbital SIF (1) and MIF (2) types indicate proximo-distal
variations within single fibers examined in serial sections. cQuantitative data from Mayr (1973) in rat extraocular muscle. dHistochemical data from cat EOM: SDH,
succinct dehydrogenase; NADH-TR, nicotinamide adenine nucleotide dehydrogenase-tetrazolium reductase; LDH, lactic dehydrogenase; Men-a-GPD, menadione-linked
a-glycerophosphate dehydrogenase; PAS, periodic acid-Schiff; AChE, acetyl-cholinesterase. Level: +/– (very low), +(low), ++ (intermediate), +++ (high), ++++
(very high).
5
6
that EOM contains two distinct forms of the em-
bryonic myosin heavy chain protein, one potentially
unique to EOM, that may represent alternative
splicing of Myh3 or an alternative gene. Myosin
isoforms also show variation along the length of
individual fibers; Myh13 is expressed only in the vi-
cinity of the neuromuscular junction, while Myh3 is
expressed both proximal and distal to this site
(Rubinstein and Hoh, 2000; Briggs and Schachat,
2002; Lucas and Hoh, 2003). The fast isoform of the
sarcoplasmic reticulum calcium ATPase (Atp2a1)
shows a similar pattern of longitudinal variation,
dropping out distal to neuromuscular junction sites
(Jacoby and Ko, 1993). A substantial number of
orbital layer fibers express the neonatal myosin
heavy chain isoform (Myh8), although it is currently
unclear whichfiber types these are (Wieczorek et al.,
1985; McLoon et al., 1999). The overall orbital SIF
Fig. 4. Ultrastructural profiles of the SIF (A) and MIF (B) muscle fibers of the orbital layer, and the red (C), intermediate (D), and
white (E) SIFs and the MIF (F) of the global layer, of the monkey lateral rectus muscle. Muscle fiber types are differentiated on the
basis of the size, number and distribution of mitochondria, the size and delineation of the myofibrils, and the extent of development of
the internal membrane system (sarcoplasmic reticulum and T-tubules). c, capillary; mn, myonucleus; s, neuromuscular synaptic ending;
a, preterminal axon. Scales: A, C, 10 mm; B, D–F, 5 mm.
57
profile is consistent with rapid, highly fatigue resist-
ant muscle contractions.
Consistent with the high mitochondrial and
oxidative enzyme content, individual orbital SIFs
are ringed by capillaries. The vascular supply of
the orbital layer and the high oxidative activity of
the SIFs may account for the high blood flow in
EOM, which exceeds that of skeletal muscle and is
surpassed only by myocardium (Wooten and Reis,
1972; Wilcox et al., 1981).
The orbital multiply innervated fiber type
Orbital MIFs (Figs. 3B and 4B, and Table 2) ac-
count for the remainder of fibers (20%) in the
Fig. 5. Ultrastructural profiles of the mitochondria (m), myofibrillar organization in the A-band (A) and I-band (I), and the de-
lineation of the myofibrils by T-tubules (t) and sarcoplasmic reticulum (sr) in the orbital SIF (A) and MIF (B), the global red (C),
intermediate (D), and pale (E) SIFs, and the global MIF (F) in the monkey lateral rectus muscle. Scale: A–F, 0.5mm.
58
orbital layer. Like the orbital SIF, this fiber type
shows considerable structural and biochemical
variation along its length. At mid-belly, the orbit-
al MIF has traits consistent with twitch contrac-
tion, exhibiting dual staining with both alkaline
(fast) and acid (slow) myofibrillar ATPase. Myo-
fibrils are larger than those of orbital SIFs and
sarcoplasmic reticulum development is moderate
(together, suggestive of slower twitch contractions)
(Fig. 5B). By contrast, proximal and distal to the
Fig. 6. Ultrastructural profiles of neuromuscular junctions associated with the orbital SIF (A) and MIF (B), the global intermediate
(C) and pale (D, E) SIFs, and the global MIF (F) in the monkey lateral rectus muscle visualized by the histochemical localization of
acetylcholinesterase. s, neuromuscular synaptic ending; a, preterminal axon; Sch, Schwann cell; mn, myonucleus. Scales: A, B, F, 2mm;
C–E, 5mm.
59
fiber mid-section orbital MIFs exhibit slow myofi-
brillar ATPase and fine structural characteristics of
slowly contracting fibers (large myofibrils and sparse
sarcoplasmic reticulum). Unlike other adult skeletal
muscle fibers, multiple nerve terminals are distrib-
uted along the myofiber length. At mid-belly, ne-
uromuscular junctions resemble those of the orbital
SIFs (Fig. 6B). By contrast, proximal and distal to
its center the nerve terminals are small and rest on
the sarcolemmal surface or in slight depressions,
with no postjunctional folds.
Based on enzyme histochemistry, orbital MIFs
exhibit only modest oxidative and weak glycolytic
capacity. Myosin heavy chain expression is consi-
stent with this profile in that mid-fiber regions
stain for the slow-twitch isoform (type I or Myh7)
and proximal/distal regions stain for both the em-
bryonic myosin (Myh3) and Myh7 (Rubinstein
and Hoh, 2000; Briggs and Schachat, 2002).
Immunoreactivity for an avian slow-tonic myosin
heavy chain also has been linked to orbital MIFs
(Pierobon-Bormioli et al., 1980). As noted above,
orbital layer fibers express the neonatal myosin
heavy chain isoform (Myh8), but it is not clear
which fiber types these are (Wieczorek et al., 1985;
McLoon et al., 1999). Orbital MIFs also exhibit
atypical myosin light chain patterns; instead of the
traditional skeletal muscle slow isoform, they ex-
press an embryonic skeletal/atrial isoform of myo-
sin light chain 1 (Bicer and Reiser, 2004).
Physiological studies suggest that orbital MIFs
exhibit twitch capability in mid-belly and non-
twitch contractions in proximal and distal fiber
segments (Jacoby et al., 1989). Collectively, the
heterogeneous features of this fiber type are unlike
any that previously has been described for skeletal
muscle, with parallels only to intrafusal (neuro-
muscular spindle) fibers, and it is difficult to draw
conclusions regarding its function.
The global red singly innervated fiber
Global red SIFs (Figs. 3C and 4C, and Table 2)
represent about one-third of the muscle fibers in the
global layer, predominating in the intermediate
zone between orbital and global layers and declin-
ing in frequency with progression into the orbital
layer. The histochemical, ultrastructural (Fig. 5C),
and myosin heavy chain expression profile of this
fiber type is similar to that of the orbital SIF, ex-
cept that it does not exhibit the longitudinal var-
iations in ultrastructure and does not co-express
the developmental myosin isoforms. Instead, global
red SIFs express the IIA myosin isoform (Myh2)
(Brueckner et al., 1996; Rubinstein and Hoh, 2000);
because of its relationship to the orbital SIF, this
fiber type may be among a population of global
fibers that expressMyh13 near their neuromuscular
junctions (Briggs and Schachat, 2002). Like its or-
bital counterpart, the global red SIF has a high
mitochondrial volume (420%) and very low myo-
fibril volume fraction (55%), suggesting that the
considerable fatigue resistance is achieved at the
cost of force reduction. Neuromuscular junction
morphology is nearly identical to that of the orbital
SIF. Collectively, these observations suggest simi-
larities with the skeletal IIA fiber type, but the very
high mitochondrial content and overall histochem-
ical profile is very different from typical IIA fibers.
The global red SIF’s profile suggests that it is fast-
twitch and highly fatigue resistant.
The global intermediate singly innervated fiber
Global intermediate SIFs (Figs. 3C and 4D, and
Table 2) comprise approximately one-fourth of the
fibers in the global layer, with rather uniform
distribution throughout this layer. Myofibrillar
ATPase and ultrastructural characteristics indicate
that this is a fast-twitch fiber type; myosin isoform
content is likely IIX (Myh1) (Rubinstein and Hoh,
2000). Moderate levels of oxidative enzymes and
anaerobic enzymes are apparent. Numerous
medium-sized mitochondria are distributed singly
or in small clusters. Myofibrillar size and sarcoplas-
mic reticulum content are intermediate between the
other two types of global SIFs (Fig. 5D). Neuro-
muscular junctions include clusters of large nerve
endings that are located in synaptic depres-
sions that include regularly spaced postjunctional
folds (Fig. 6C). Overall, this profile fits that of a
fast-twitch fiber with an intermediate contraction
speed and level of fatigue resistance, probably
lying between global red and white SIFs.
60
The global white singly innervated fiber
Global white SIFs (Figs. 3C and 4E, and Table 2)
comprise about one-third of the global layer. Global
white SIFs exhibit modest levels of oxidative en-
zymes, high anaerobic metabolic capacity, and a
fast type ATPase profile. This fiber type likely ex-
presses type IIB myosin heavy chain (Myh4)
(Rubinstein and Hoh, 2000). There are few, small
mitochondria that are singly arranged between the
myofibrils (Fig. 5E). Neuromuscular junctions are
the most elaborate of any of the six EOM fiber
types. Multiple axon terminals are clustered togeth-
er in deep depressions of the sarcolemma; post-
junctional folds are regular, numerous, and deep
(Fig. 6D, E). The overall fiber profile is consistent
with a fast-twitch type that is used only sporadically
because of low fatigue resistance.
The global multiply innervated fiber
Global MIFs (Figs. 3C and 4F, and Table 2) con-
stitute the remaining 10% of fibers in the global
layer.These fibers contain very few, small mito-
chondria that are arranged singly between the myo-
fibrils. Myofibrils are very large and sarcoplasmic
reticulum development is so poor that myofibril
separation is often indistinct (Fig. 5F). The large
myofibrils mean that the calcium source, the sarco-
plasmic reticulum, and the contractile filaments are
spatially far apart, resulting in very slow contrac-
tions. Consistent with slow excitation–contraction
coupling in this fiber type, the fast calcium ATPase
found in all other EOM fiber types is absent from
global MIFs (Jacoby and Ko, 1993). The ultra-
structural profile of this fiber resembles that of
slow, tonic muscle fibers in amphibians. Global
MIFs express slow-twitch (type I or Myh7)
(Brueckner et al., 1996; Rubinstein and Hoh,
2000), but do not appear to be immunoreactive
for avian slow-tonic myosin heavy chain (Pierobon-
Bormioli et al., 1980). There are variable reports
that it expresses the a-cardiac myosin heavy chain
isoform (Myh6). Global MIFs express the tradi-
tional skeletal muscle slow isoform of myosin light
chain 1, but not the skeletal/atrial isoform found in
orbital MIFs (Bicer and Reiser, 2004).
There are numerous small superficial grape-like
endings distributed along the longitudinal extent
of individual fibers of global MIFs (Fig. 6F).
A novel type of sensory nerve terminal, the myo-
tendinous cylinder or palisade ending, is associated
with the myotendinous junction of this fiber type.
Like amphibian muscles, the global MIF type
exhibits a slow graded, non-propagated response
following either neural or pharmacologic activa-
tion (Chiarandini and Stefani, 1979). The finding
of a phylogenetically primitive muscle fiber type in
one of the fastest skeletal muscles is difficult to
reconcile, unless one considers a potential role in
either very fine foveating movements of the eye or
as part of a specialized proprioceptive apparatus
(Ruskell, 1978) (cf. Chapter 3).
Differences in EOM fiber types in the same and
different species
Differences between the rectus and oblique muscles
in the same species appear to be largely attributable
to variations in the total number of fibers in each
muscle. Such muscle-to-muscle variability in myo-
fiber number, however, is primarily the result of
differences in orbital, but not global, layers (Oh
et al., 2001). These authors attributed this finding to
rectus muscle sharing of a similar mechanical load
on the eye-mover global layers, but rectus muscle
dissimilarities in load on pulley-mover orbital lay-
ers, because of pulley differences in elasticity.
EOMs of the same species can differ in relative
proportions of the six muscle fiber types (Ringel
et al., 1978; Vita et al., 1980; Carry et al., 1982;
McLoon et al., 1999). Similar to the fiber count
data, human EOMs show the largest same-species
variation in the orbital layer (medial recti having
the highest and lateral recti the lowest percentage of
orbital SIFs; Ringel et al., 1978). Finally, while
complexity of myosin heavy chain expression may
be confined to the orbital layer in rat (i.e., global
layer fibers may express single myosin isoforms;
Rubinstein and Hoh, 2000), myofibers of the global
layers of rabbit and human EOM may be more
heterogeneous in myosin heavy chain expression
patterns (McLoon et al., 1999; Briggs and Schachat,
2002; Kjellgren et al., 2003b). Taken together,
61
individual muscle variations in the proportion of
different muscle fiber types, and variability in myo-
sin expression patterns of single types, might ex-
plain differences in the rate- and tension-related
contractile properties of different EOMs (Meredith
and Goldberg, 1986).
Differences between the same muscle in different
species are more difficult to assess, since compar-
isons between studies are based on the interpreta-
tion of comparable fiber types with different
nomenclatures and examined by different meth-
ods. Based upon the range of data published to
date, it is reasonable to conclude, however, that
analogous fiber types exist across mammalian
species. There are, however, suggestions that fib-
er types in human EOMs may be more complex
than those of other species (Kjellgren et al., 2003a,
b). While the number of muscle fibers, their diam-
eters, and possibly the proportion of different
muscle fiber types may vary between species, the
extent of development of individual fiber types al-
so may be an important factor that underlies their
physiological differences.
The most dramatic difference between species is
in the morphology of the orbital SIF. While the
contractile elements of this fiber are similar
between species, mitochondrial content varies con-
siderably (Fig. 7). Orbital SIFs appear to attain
their most extensive mitochondrial development in
the primate. Comparisons between SIFs of the
rabbit and cat suggest that orbital SIF differences
in mitochondrial content may not be related solely
to frontal versus lateral eye placement. A more
parsimonious interpretation is that the morpholo-
gy of this fiber type is directly related the recent
linkage of orbital layer to muscle pulley function
(Demer et al., 2000), with increased oxidative func-
tion and fatigue resistance necessary for the greater
pulley development, wider oculomotor range, and
reliance upon eccentric eye positions in primates
versus rodents (Khanna and Porter, 2001). Consi-
stent with this view, high blood flow may not be a
general feature of EOMs in all species, but rather
varies between species and is especially high in
those with greater ocular motility (Wilcox et al.,
1981). By contrast, differences between species in
the morphology of the orbital MIF appear to be
more subtle. The most apparent difference between
species in the global muscle fiber types is their
diameters (although the ratio of global MIF to
global SIF diameter appears to be considerably
higher in rodents than in higher species). Collec-
tively, differences in global myofiber size and
number could account for observed differences in
isometric tension in the cat (Barmack et al., 1971)
and monkey (Fuchs and Luschei, 1971).
An integrated view of EOM biology
Current knowledge of EOM biology is clearly in-
complete. For example, there is a complex pattern
of myofibril size variation in both orbital and glo-
bal fiber types (Davidowitz et al., 1996a, b) that
has not yet been accounted for in modeling EOM
function. However, new data from approaches
ranging from orbital anatomy to EOM cell and
molecular biology now allow a more integrated
view of EOM. Here, we review the implications of
new data and concepts in EOM and oculomotor
physiology and EOM molecular biology and es-
tablish the importance of arriving at an integrated
view of EOM myofiber and whole muscle biology.
Insights from EOM and oculomotor physiology
One goal of correlative anatomical, molecular, and
physiological studies of EOM has been to uncover
any association of specific muscle fiber types with
defined eye movement functions. The segregation
of function among different EOM motor unit
types has been a long-debated issue. An early con-
cept of EOM suggested that the distinct EOM fiber
types might be responsible for the different classes
of eye movement. Oculomotor motoneuron activ-
ity in alert animals (Robinson, 1970) and intraop-
erative electromyographic studies (Scott and
Collins, 1973), however, showed that all motoneu-
rons and all EOM fiber types participate in all eye
movement classes. These findings supported the
alternative hypothesis, that the heterogeneity of
the six EOM fiber types is a consequence of their
recruitment at specific eye positions, thereby
requiring a range of contractile and fatigability
properties.
62
Skeletal muscles are organized into motor units
— defined as a single motoneuron plus the muscle
fibers that it innervates. Motor unit size is the
number of muscle fibers that are innervated by an
average motoneuron. The ability of a skeletal mus-
cle to increment force then is dependent upon the
range of available