Download Structure-function correlations in the human medial rectus

A n understanding of extraocular muscle function requires not only the anatomic study of static, fixed specimens, but also the detailed evaluation of dynamic
muscle contractile properties and paths at different
gaze
positions-innervation levels (see refs. 1 and 2).
John D. Porter*^ Vadims Poukens,%$
Using contemporary, high-resolution imaging ivchRobert S. Baker,,f and Joseph L. Demer§
niques, individual muscles are observed to swinsj in
Purpose. Fibroelastic pulleys function like the trochlea toward the optic nerve with contraction and outv ard
with relaxation.3 The normal occurrence of muscle
to fix the position and pulling direction of the recti
excursions in the radial direction as they shorten or
extraocular muscles within the orbit. This study characterized the fine structure of the human medial rectus
lengthen most likely is not relevant, and therefore is
muscle pulley.
not accounted for, in the neural programming of eye
Methods. Human medial rectus muscle pulley tissue was movements. In contrast to the relative mobility in the
radial direction, recti muscle paths are nearly immobidissected at autopsy, immersed in aldehydefixativesolulized over the full range of gaze, with minimal sidetion, and processed for and examined with light and
slip along the surface of the globe in a direction orelectron microscopy.
34
Results. Pulley structures were located within posterior thogonal to muscle pulling directions. The muscle
path stabilization was predicted by biomechanical
Tenon's fascia, closely surrounding the medial rectus
modeling56 and was confirmed using computerized
muscle. Pulleys were comprised of a dense collagen matomography in humans,7 conventional x-ray imaging
trix with alternating bands of collagen fibers precisely
in alert monkeys,4 and magnetic resonance imaging
arranged at right angles to one another. This threein humans.3'8
dimensional organization most likely confers high ten-
Structure-Function Correlations in
the Human Medial Rectus
Extraocular Muscle Pulleys
sile strength to the pulley. Elastin fibrils were interspersed in the collagen matrix. Fibroblasts and mast
cells were scattered throughout the relatively acellular
and avascular collagen latticework. Connective tissue
and smooth muscle bundles suspended the pulley from
the periorbita. Smooth muscle was distributed in small,
discrete bundles attached deeply into the dense pulley
tissue.
The orbit contains an organized system of connective tissues.9"11 Anatomic studies of human orbits have
shown that the stabilization of rectus muscle paths is
mediated by identifiable connective tissue pulleys that
are elastically suspended from the orbital walls.12 Fibroelastic pulleys, consisting of connective tissue
sheaths in posterior Tenon's fascia, surround the recti
Conclusions. Fine structural observations confirm the ex- extraocular muscles and function like the trochlea.
The pulleys thus serve as mechanical origins that fix
istence and substantial structure of a pulley system in
the position and pulling direction of the muscles
association with the medial rectus extraocular muscle.
within
the orbit.12 Extraocular muscle pulleys have a
The presence of pulleys must be considered in models
of the oculomotor plant. The cytoarchitecture and
significant effect on orbital mechanics. The existence
placement of pulleys suggest that they are internally
of muscle pulleys also has an effect on strabismus surrigid structures and are consistent with the idea that
gery outcomes.8 The current study used fine structural
they determine functional origins for the extraocular
analysis of human extraocular muscle pulleys to exmuscles. However, the nature of the connective tissue—
tend understanding of the role of the peripheral ocusmooth muscle struts suspending the pulley system to
lomotor
plant in eye movement control.
the orbit supports the notion that the pulley position,
and thus the vector force of the eye muscles, may be
adjustable. Invest Ophthalmol Vis Sci. 1996; 37:468472.
From the Departments of * Anatomy and Neurobiology and f Ophthalmology,
University of Kentucky Medical Center; and from the Departments of%Palhology
and Laboratory Medicine, §Ophthalmology and Neurology, and the $Jules
Stein Eye Institute, University of California, Los Angeles.
Presented in part at the annual meeting of the Association for Research in Vision
and Ophthalmology, Fort lMuderdale, Florida, May 1995.
Supported by National Eye Institute grants EY09834 (pP) and EY08313 (JLD)
and by Research to Prevent Blindness. JDP is the recipient of a Research to Prevent
Blindness ljew R. Wasserman Merit Aiuard.
Submitted for publication September 14, 1995; revised November 8, 1995; accepted
November 9, 1995.
Proprietary interest category: N.
Reprint requests: John D. Porter, Department of Anatomy and Neurobiology,
University of Kentucky Medical Center, 800 Rose Street, Ijixington, KY 405360084.
METHODS. All human studies adhered to the
tenets of the Declaration of Helsinki and were approved by institutional review boards, and informed,
written consent was obtained. In this study, medial
rectus muscle pulleytissuewas dissected from exenterated fresh adult orbits at autopsy with authorization
by next of kin. Pulleys are associated with all four
recti muscles.12 The most highly developed pulley in
humans, that associated with the medial rectus, was
selected for analysis. Pulleys were divided to enhance
fixative penetration and were immersed in 4% glutaraldehyde fixative solution in 0.1 M phosphate buffer
for 48 hours and then processed by routine methods
for light and electron microscopy, as described in de-
468
Investigative Ophthalmology & Visual Science, February 1996, Vol. 37, No. 2
Copyright © Association for Research in Vision and Ophthalmology
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:\
FIGURE i. light
(A,B)
and
^
electron (C,D) photomicro- J,"
graphs of the dense connective
tissue of the orbital side of a
human medial rectus muscle
pulley. Note muscle fibers of
the adjacent medial rectus
(arrow) and the dense collagen
matrix of the pulley proper
with embedded elastin filaments (AJB). The general organization of the pulley tissue
proper is a dense, relatively
acellular collagen matrix. Alternating bands of collagen fibers
were arranged precisely at right
angles to one another (C),
likely conferring high tensile
strength to the pulley (x-s indicates cross-sectioned collagen;
I-s indicates longitudinally oriented collagen). Elastin fibrils
(e) were interspersed in the
collagen matrix and were most
densely distributed in regions
adjacent to the medial rectus.
Fibroblasts (f in C) and mast
cells (m in D) also were scattered at intervals throughout
the dense pulley matrix. Scale
bars = 50 pirn (A), 25 /xm (B),
5//m ( C ) , 2 ^ m (D).
tail previously.13 Briefly, tissues were postfixed in 1%
osmium tetroxide, stained en bloc with 0.05% uranyl
acetate, dehydrated in a graded series of methanols
followed by propylene oxide, embedded in epoxy
resin, and sectioned for light and electron microscopy.
Semithin (1 /im) sections were stained with toluidine
blue and examined with bright-field microscopy; ultrathin (90 nm) sections were stained with uranyl acetate
and lead citrate and examined using a Hitachi (Mountain View, CA) HM-7000 electron microscope. Pulley
smooth muscle cytoarchitecture and organization
were compared with those of specimens of Miiller's
muscle that were surgically excised in cases of congenital ptosis and were processed similarly.
RESULTS. Rectus muscle pulley sleeves are continuous with the tough peripheral portion of posterior
Tenon's fascia and become incomplete slings both
anteriorly and posteriorly. Sleeves are stabilized by the
fibromuscular septae extending from the pulleys
proper to the orbital walls and to adjacent pulleys by
way of posterior Tenon's fascia. Details of the general
pulley architecture have been published elsewhere.'2
In this study, analyses were directed to the fine structure of the dense, orbital portions of the medial rectus
pulley sleeve and the "struts" that anchor the pulley
to the periorbita and orbital walls.
The core structure of the pulley was a densely
packed collagen matrix (Figs. 1A, IB). Elastin fibrils
were interspersed in the collagen matrix and were
most densely distributed on the orbital side of the
pulley, immediately adjacent to the extraocular muscle. There did not appear to be any substantive, specialized covering of either the internal surface of the
pulley or the external surface of the muscle tendon
as it passed through the pulley. It has been suggested
that entire recti tendons slide smoothly within the
pulley sleeves by the telescoping of loose connective
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470
Investigative Ophthalmology & Visual Science, February 1996, Vol. 37, No. 2
FIGURE 2. light (A) and electron (B,C) photomicrographs
of the discrete smooth muscle
bundles that extend radially
from and are involved in suspension of the medial rectus
pulley. Smooth muscle cells
were distributed into bundles
(s), usually 30 to 150 /tm in diameter, which were tightly encased in collagen and attached
into die dense pulley tissue.
Muscle cells (n denotes representative nuclei) were segregated into small, discrete bundles. Fine structural features of
individual smooth muscle cells
in pulleys (C) were identical
witfi diose in other muscles,
with few, scattered mitochondria (m), caveolae (open
arrows), and dense bodies-attachment plaques {arrowheads).
Note that collagen (c) surrounds individual smooth muscle cells with no direct cell-cell
contact Scale bars = 50 /j,m
<A), 5/xm (B), 0.5 Mm (C).
tissue that surrounds the tendon.12 Current observations are not inconsistent with this hypothesis. At the
ultrastructural level, pulleys consisted of alternating
lamellae of collagen fibers precisely arranged at right
angles to one another (Fig. 1C), likely conferring high
tensile strength. Fibroblasts and mast cells were interspersed throughout the collagen latticework (Figs. 1C,
ID). The dense pulley tissues had a low vascular content.
Connective tissue and smooth muscle bundles
provided a suspension system for the pulleys, extending radially away from the globe to anchor the
pulley directly to the periorbita (Fig. 2). Smooth muscle was distributed in discrete bundles, usually 30 to
150 fj,m in cross-sectional diameter, that were tightly
encased in collagen and were attached into the dense
portion of the pulley tissue. This arrangement contrasted with the thin, wide sheet of smooth muscle
fibers, encased in a loose connective tissue matrix,
that characterized Muller's muscle (Fig. 3). In both
Muller's muscle and the pulley struts, individual
smooth muscle cells were separated by wide extracellular spaces occupied by collagen, and neither muscle
exhibited gap junction contacts between adjacent cells
(Fig. 2C). The cytoarchitectural features of individual
smooth muscle cells (i.e., contractile filaments, caveolae, dense bodies) in the pulley struts were identical
to those in other muscles, including Muller's muscle.
Although the fixation of human pulley tissues was
moderately good, the necessary reliance on autopsy
material for these studies precluded identification of
smooth muscle-associated autonomic nerve terminals14'15 at the electron microscopic level.
DISCUSSION. Extraocular muscle pulleys, although compliant, stabilize the position of individual
recti muscles within the orbit The existence of the
pulleys requires alteration of long-held concepts of
orbital dynamics and must be considered in modeling
of the oculomotor plant. Radial movement of the recti
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FIGURE 3. Electron photomicrograph of Miiller's muscle. As
is the smooth muscle of the recti muscle pulleys, the smooth
muscle cells of Miiller's muscle are isolated from one another (n denotes representative nuclei). However, the discrete bundles of smooth muscle associated with the pulleys
contrast with the smooth muscle sheet seen in Miiller's muscle. This organizational difference may facilitate more efficient neural activation of the smooth muscle associated with
the pulleys. Associated collagen is less dense than in pulleys.
Scale bar = 5 fj,m.
muscles, toward and away from the optic nerve, is
allowed by the arrangement of orbital connective tissues. By contrast, the side-slip of recti muscle bellies
across the globe is markedly restricted.3 Current data
support the notions that mechanically substantial pulleys exist in Tenon's capsule and that these are capable of directing muscle paths during gaze changes.
Not unlike the trochlea that anchors the superior
oblique, the cytoarchitecture of medial rectus pulleys
suggests that the fibroelastic muscle sheaths are highly
stiff structures. Their relatively acellular nature and
the presence of dense collagen arrays oriented at right
angles to one another confer substantial three-dimensional strength to the pulley, precisely at the site of
attachment of its suspension system. Ultrastructural
data suggest that the pulleys are sufficiently stiff to
stabilize the rectus muscles during large changes in
gaze, as was independently demonstrated with magnetic resonance imaging.3 i2
The contrast between the anchoring system of the
recti muscle pulleys and the trochlea suggests a difference in the two strategies of establishing functional
muscle origins. Rigid anchoring of the trochlea supports the view that it mediates a fixed, passive change
in superior oblique line of force. By contrast, the nature of the connective tissue—smooth muscle struts
suspending the pulley system to the orbit supports the
hypothesis that the pulley position, and thus the vector
force of the eye muscles, may be adjustable by either
passive stiffness or active (e.g., smooth muscle innervation, hormonal) mechanisms. Although orbital
smooth muscle is not uncommon in mammals, it is
unlikely that the pulley support structure is vestigial.
Phylogenetic studies (Demer JL, unpublished, 1995)
suggest that the pulleys are of particular importance in
humans. Moreover, an intricate innervation pattern,
including rich sympathetic, parasympathetic, and nitroxidergic innervation1415 to pulley smooth muscle,
further supports the hypothesis of a refined role in eye
alignment, movement, or both. Innervation of smooth
muscle in the pulley struts, albeit slower than skeletal
muscle activation mechanisms, may alter the functional muscle origin in accordance with gaze
changes.1415 Despite substantial temporal differences
in excitation-contraction coupling for skeletal versus
smooth muscle, coordinated function of Muller's muscle and the levator palpebrae superioris does occur in
the control of vertical eyelid position. Applying a similar skeletal-smooth muscle interactive scheme to the
recti muscle pulleys, the smooth muscle in the pulley
struts might serve to alter dynamically pulley position
during gaze changes. Either innervation or an intrinsic contractile response to stretch could provide temporally appropriate changes in pulley position. Alternatively, slow, attention-related changes in smooth
muscle force in the pulley struts might serve simply to
maximize extraocular muscle force generation in the
alert state.
Finally, the presence of pulleys, in association with
the rectus extraocular muscles, may have implications
for the computations required of brainstem circuitry in
the neural control of eye movements. Although some
high level oculomotor centers clearly operate in a spatial
coordinate scheme,16 the motor command is decomposed into signals appropriate for activating individual
muscles that must relate to retinocentric coordinates.
Taken together, the properties of the recti extraocular
muscle pulleys and the role they play in stabilization of
muscle paths must be understood to resolve contemporary questions regarding the axes of ocular rotation during reflexive eye movements.17"19
Key Words
extraocular muscle, oculomotor, orbital mechanics, strabismus, Tenon's capsule
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Investigative Ophthalmology & Visual Science, February 1996, Vol. 37, No. 2
Acknowledgments
The authors thank Mary Gail Engle and Olga Itkis for technical assistance. They also thank Dr. Paul May for helpful
discussions concerning the interpretation of pulley function.
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