throbber
HISTOLOGY
`
`of the
`
`HUMAN EYE
`
`An Atlas and Textbook
`
`W. B. SAUNDERS COMPANY
`
`Petitioner - New World Med iiii
`
`Philadelphia
`
`London
`
`Toronto
`
`197 1
`
`Petitioner - New World Medical
`Ex. 1010, p. 1 of 21
`
`

`

`W. B. Saunders Company: West Washington Square
`Philadelphia, Pa. 19105
`12 Dyott Street
`London, WC1A 1DB
`1835 Yonge Street
`Toronto 7, Ontario
`
`Histology of the Human Eye
`
`SBN
`
`0-7216-4720-0
`
`© 1971 by W. B. Saunders Company. Copyright under the International Copyright Union.
`All rights reserved. This book is protected by copyright. No part of it may be reproduced,
`stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical,
`photocopying, recording, or otherwise, without written permission from the publisher. Made
`in the United States of America. Press of W. B. Saunders Company. Library of Congress
`catalog card number 78-135327.
`
`Print No.:
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`9
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`8
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`7
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`6
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`5
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`4
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`3
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`2
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`1
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`Petitioner - New World Medical
`Ex. 1010, p. 2 of 21
`
`

`

`CHAPTER FOUR
`
`136
`branch more often and form extensive intercommunications. The fibrils are
`not so uniformly spaced as they are in the cornea and there is less ground
`substance. Posteriorly the fibrils assume dimensions more like those in the
`sclera, their diameter being between 700 and 1000 A. The fibroblasts of the
`limbal stroma are like those of the cornea and sclera. Only occasional macro-
`phages and leukocytes are seen here.
`Most of the vessels encountered in the limbal stroma are the veins of
`the deep and intrascleral plexuses. Small arterial channels are found through-
`out the stroma and a net of small arteries appears in the region of
`Schlemm's canal, but those vessels do not communicate directly with the
`lumen of the canal.
`Myelinated and unmyelinated nerves are seen throughout the limbal
`stroma, most of them being branches of the ciliary nerves which are destined
`for the cornea.
`
`AQUEOUS OUTFLOW APPARATUS (Figs. 4-16 and 4-17)
`
`The limbus contains structures which are specially developed for the
`removal of aqueous humor. The elements involved in removal of the
`aqueous humor are mostly found in the internal scleral sulcus. The outflow
`apparatus is composed of tissue derived from the cornea, sclera, iris, and
`ciliary body and will be described as follows:
`
`1. Schlemm's canal and collector channels
`a. Schlemm's canal
`b. External collector channels
`c. Internal collector channels
`2. Trabecular meshwork
`a. Corneoscleral meshwork
`b. Uveal meshwork
`c. Pectinate fibers or iris processes
`3. Scleral spur
`4. Deep corneolimbus
`5. Innervation
`
`Figure 4-16. Drawing of the aqueous outflow apparatus and adjacent tissues.
`Schlemm's canal (a) is divided into two portions. An internal collector channel (Sondermann)
`(b) opens into the posterior part of the canal. The sheets of the corneoscleral meshwork (c)
`extend from the corneolimbus (e) anteriorly to the scleral spur (d). The rope-like components of
`the uveal meshwork (f) occupy the inner portion of the trabecular meshwork; they arise in the
`ciliary body (CB) near the angle recess and end just posterior to the termination of Descemet's
`membrane (g). An iris process (h) extends from the root of the iris to merge with the uveal
`meshwork at about the level of the anterior part of the scleral spur. The longitudinal ciliary
`muscle (i) is attached to the scleral spur but has'a portion which joins the corneoscleral mesh-
`work (arrows). Descemet's membrane terminates within the deep corneolimbus. The corneal
`endothelium becomes continuous with the trabecular endothelium at (j). A broad transition zone
`(double-headed arrows) begins near the termination of Descemet's membrane and ends where
`the uveal meshwork joins the deep corneolimbus.
`
`Petitioner - New World Medical
`Ex. 1010, p. 3 of 21
`
`

`

`THE LIMBUS
`
`137
`
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`A
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`41
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`6
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`5
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`Figure 4-16. See legend on opposite page.
`
`Petitioner - New World Medical
`Ex. 1010, p. 4 of 21
`
`

`

`138
`
`ti
`
`•
`
`CHAPTER FOUR
`
`4
`
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`
`•
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`dr.7.
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`4.1•0"
`
`4:44-1-
`
`Figure 4-17. Light micrograph of the aqueous outflow apparatus. Schlemm's canal (a) is
`split into two portions. The external wall of the canal is relatively smooth in comparison with
`the inner wall. The inner canal wall is identified by single arrows. The scleral spur (b) with its
`denser collagenous tissue is seen posteriorly. The empty intertrabecular spaces (double arrows)
`are formed by the sheets of the corneoscleral meshwork. The thin cords of the uveal meshwork
`are adjacent to the anterior chamber; one cord (c) is shown. (x 310.)
`
`Schlemm's Canal and the Collector Channels
`Schlemm's Canal (Figs. 4-18 to 4-29). This circular venous channel
`lies in the outer portion of the internal scleral sulcus. The external wall of
`the canal is located quite close to the limbal stroma but is separated from it
`by the thin layers of connective tissue that form the canal wall. The internal
`wall of the canal of Schlemm is adjacent to the deepest part of the corneo-
`scleral meshwork. The deep sclera is close to the posterior boundary of
`Schlemm's canal, and on its anterior side are the sheets of the corneoscleral
`meshwork.
`The ring formed by the canal measures 36 mm. in circumference
`(McEwen, 1965), and it has a flattened elliptical cross-section. Its meridional
`width varies between 350 and 500 gm. in adults, being somewhat smaller in
`children, and the lumen frequently becomes very narrow or even splits into
`branches which enclose islands of tissue. Salzmann (1912) likened this
`configuration to that of a river that is subdivided by islands along its course.
`The surface of the canal is varicose, the varicosities having cross-sectional
`shapes from round to oval, or even triangular (Ashton, 1951). When the
`shape is triangular, the base is posterior and measures 50 gm. in width,
`while the anterior apex narrows to 5 or 10 gm.
`A thin connective tissue wall surrounds the endothelial lining of
`Schlemm's canal. On the external side the wall is 5 to 10 gm. in thickness
`and can be differentiated easily from the adjacent limbal stroma by its
`cellularity and large deposits of finely fibrillar material. The greater part of
`this layer is composed of fibroblasts having numerous arrays of rough-sur-
`faced endoplasmic reticulum, a well developed Golgi apparatus and many
`mitochondria. It is likely that the fine granular material present near these
`fibroblasts is synthesized by the cells. If this material is tropocollagen, it will
`undergo further polymerization to form the mature collagen fibrils. The
`collagen fibrils in the external adventitia resemble those of the corneal
`stroma, measuring approximately 300 A. in cross-sectional diameter. The
`fibrils are irregularly dispersed in an abundant matrix composed of a slightly
`osmiophilic, amorphous ground substance.
`
`Petitioner - New World Medical
`Ex. 1010, p. 5 of 21
`
`

`

`THE LIMBUS
`
`139
`
`Figure 448. Composite electron micrograph of Schlemm's canal. The anter-
`ior canal is near (a), the inner side is at (b) and the limbal stroma is at (c). The canal
`has a length of 500 Am. and an average width of 40 az.m. Numerous red blood cells
`occupy the lumen of the canal, probably as a result of backflow into the canal at
`surgery. An internal collector channel (d) or canal of Sondennann is seen at the
`bottom of the photograph near the posterior canal. The external wall of the canal is at
`(e) and the internal wall is at (0. In this photograph the inner wall of the canal shows
`no giant vacuoles in the endothelium. The bridging of the intertrabecular spaces by
`endothelial cells and subdivisions of the trabecular sheets is evident at (g). (x 760.)
`
`•
`
`41
`J
`
`4
`
`•
`
`•
`
`.1
`
`Petitioner - New World Medical
`Ex. 1010, p. 6 of 21
`
`

`

`140
`
`CHAPTER FOUR
`
`Intrascier
`
`Intern,/
`
`e/0
`
`Gay
`
`eo co
`
`me
`Vr
`
`O.
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`2.
`cc`
`t.e
`
`Figure 4-19. Schematic drawing showing the circular course and related vessels of the
`canal of Schlemm. The canal divides into two or more portions intermittently. The drawing is
`divided into four portions by the dotted lines. The internal collector channels of Sondermann are
`labeled in the upper right sector as they extend into the trabecular meshwork. The external
`collector channels are seen in the upper and lower right sectors, arising from the canal and
`uniting with the deep intrascleral plexus or extending directly to the episcleral veins. The deep
`and intrascleral venous plexuses are external to the canal.
`In the upper left sector an aqueous vein (1) arises from the deep scleral plexus and
`another (2) arises from Schlemm's canal and runs directly to the episcleral venous plexus.
`External collector veins are seen to arise from the canal and join the deep sclera' plexus.
`In the lower left sector the arteries of the deep sclera are seen to be in close relation to the
`canal of Schlemm.
`
`Petitioner - New World Medical
`Ex. 1010, p. 7 of 21
`
`

`

`THE LIMBUS
`
`141
`Polymorphonuclear leukocytes, macrophages and mast cells are seen
`occasionally in this narrow cellular connective tissue layer. It is surrounded
`by a transition zone measuring 20 to 30 Am. in thickness and composed of 8
`to 10 lamellae of collagenous tissue. These collagenous lamellae run in all
`directions and are separated from each other by long fibroblasts. The colla-
`gen fibrils of the lamellae gradually increase in cross-sectional diameter
`from 300 A. to 800 to 1000 A. in diameter so that they come to resemble
`scleral collagen.
`The cell wall internal to Schlemm's canal continues posteriorly
`around the wall of the canal and joins the external wall. This internal wall
`has been studied for many years by light microscopists, who noted the
`presence of many cells and a complete absence of trabecular spaces in the
`zone adjacent to the canal. It has been called the pore tissue by Flocks
`(1956), the cribriform area by Rohen (1961, 1963, 1964), and the juxtacanalicu-
`lar connective tissue by Fine (1966). If a title has to be applied, juxtacanalicu-
`lar tissue is most satisfactory, but we prefer to consider it as the inner wall of
`Schlemm's canal.
`The structure and thickness of this canal wall vary in different sec-
`tions along its sinuous outline. Many areas are seen in the wall where the
`ground substance has been extracted during the processing of the tissue,
`causing further changes in its character. Extracted areas of this type have
`been mistaken in the past for trabecular spaces, introducing an additional
`error in estimation of the actual thickness of the canal wall. In general, this
`layer measures between 10 to 20 p.m. in thickness between the "basement
`membrane" of the endothelium and the nearest intertrabecular space. In
`well fixed specimens a complete endothelial layer is generally demonstrable
`at the junction of the outermost trabecular space with the canal wall.
`The relationship between the trabecular spaces, the cell wall and the
`canal of Schlemm is as follows: (1) a layer of endothelium lines the outer-
`most trabecular space; (2) next to this is found connective tissue of the canal
`wall which is composed of the same cells, collagen, tropocollagen and
`amorphous ground substance as we have described in the external canal
`wall; and (3) the endothelium of Schlemm's canal and its basement mem-
`brane. However, even in well fixed specimens there may be a few areas
`where the first and second components are lacking, and in such regions only
`the endothelium of the inner canal wall and its basement membrane sepa-
`rate the canal of Schlemm from the nearest intertrabecular space.
`The lumen of Schlemm's canal is lined by an endothelium which has
`a rather smooth luminal surface everywhere except for its sinuous inner side.
`Most of the endothelial cells are small, having an average diameter of 10 imn.
`and a thickness of 0.2 µ,m. (Holmberg, 1965). Those along the inner wall,
`however, have a diameter of 20 to 50 p.m. An endothelial basement mem-
`brane has been described, especially at the inner wall of the canal (Garron et
`al., 1958). This membrane is quite different from basement membranes found
`in other tissues, such as those of the corneal epithelium and of capillary
`endothelium. It is poorly defined, inconstant, frequently interrupted and of
`variable thickness; it is often separated from the endothelium by an irregular
`space. The lateral walls of the endothelial cells are joined by tight junctions,
`mainly zonulae occludentes, near their luminal surfaces. The points of mem-
`brane fusion are unusually small, measuring between 100 and 200 A., and
`occasionally the intercellular space is not closed by a tight junction.
`
`Petitioner - New World Medical
`Ex. 1010, p. 8 of 21
`
`

`

`142
`
`I
`
`!•
`
`CHAPTER FOUR
`
`a
`
`iffy
`
`h
`
`Figure 4-20. Schlemm's canal, internal wall. The lumen of the canal is at (a) and the
`nearest trabecular space is at (b). One endothelial cell lining the canal contains a giant vacuole
`(c) which measures 2.5 um. in diameter and protrudes into the lumen of the canal. Four
`endothelial cells (d) line the inner canal wall. The trabecular space (b) is lined by portions of
`
`Petitioner - New World Medical
`Ex. 1010, p. 9 of 21
`
`

`

`THE LIMBUS
`
`143
`The cytoplasm of these endothelial cells is mainly characterized by its
`content of filaments and free ribosomes. The mitochondria are very small,
`and the Golgi apparatus and profiles of rough-surfaced endoplasmic reticu-
`lum are seen only occasionally. Numerous pinocytotic vesicles, similar in
`size and distribution to those seen in the endothelium of capillaries, are
`found along the cell membranes of this endothelium.
`Many of the cells along the internal canal wall possess cytoplasmic
`vesicles or vacuoles of extraordinary dimensions and of specific distribution.
`These have come to be known as giant vacuoles and are found only in the
`cells of the inner wall of Schlemm's canal. The vacuoles are outlined by a
`single membrane, with the largest vacuole measuring up to 14 pm. in length
`by 5 gm. in width. Holmberg (1965) made serial sections of 10 pm. portions
`of canal wall and found an average of 0.5 vacuoles per 10 p.m. The range for
`six eyes was from 0.3 to 0.9 vacuoles for 10 p.m. These giant vacuoles have
`been the subject of numerous studies, but their role and importance in
`aqueous humor transport into the lumen of Schlemm's canal is not entirely
`clear. In some early studies the vacuoles were shown to have an opening
`into the lumen of Schlemm's canal measuring about 0.3 to 2.0 p.m. in
`diameter. A number of investigators (Speakman, 1960; Rohen, 1961; Holm-
`berg, 1959, 1965) have also seen openings from these vacuoles into the
`nearest trabecular spaces. It has been suggested that the vacuoles might
`provide a direct pathway for the movement of aqueous humor from the
`innermost trabecular space into the canal of Schlemm (Garron et al., 1958;
`Garron and Feeney, 1959; Holmberg, 1959, 1965; Leeson and Speakman,
`1961; Spelsberg and Chapman, 1962; Iwamoto, 1967a; ICayes, 1967; Vegge,
`1963, 1967; and Tripathi [Rhesus], 1968).
`The presence of the canal wall as a practically continuous layer be-
`tween the endothelial lining of the canal and the nearest trabecular space
`makes it difficult to believe that the vacuoles can provide a constant pathway
`for the flow of aqueous humor. The vacuoles may actually open into the
`connective tissue, but in recent studies they have not been observed to open
`into the nearest trabecular space. Feeney and Wissig (1966), using an elec-
`tron-opaque tracer (ferritin), showed that the vacuoles are not constantly
`open. When tracer material was perfused into the anterior chamber it accu-
`mulated in high concentration within some vacuoles, while it was entirely
`absent in others. It seemed to these investigators that the vacuoles must
`
`Figure 4-20. Continued.
`two endothelial cells (e). One cell branch almost crosses the intertrabecular space to join the
`endothelial cell of a trabecular sheet. The cells lining the spaces of the trabecular meshwork
`are thicker and more extensive than those lining Schlemm's canal.
`The inner wall of the canal (f) includes all the tissue between the endothelium (d) of the
`canal and the endothelium (e) of the nearest trabecular space (b). The canal wall contains
`numerous fibroblasts (g) and thin collagen fibrils (h). The collagen fibrils measure 300 A. in
`diameter and most often are seen in cross-section when the sections are meridional. Adjacent to
`the canal some collagen fibrils are in close contact with its endothelium (arrows). This arrange-
`ment is similar to that found in lymphatic channels. The endothelial cells lack a basement
`membrane in this portion of the canal for 20 gm. At (j) a fibroblast appears to have what has
`been described as a "basement membrane." The abundant ground substance of the canal wall
`has been extracted during preparation of the tissues, leaving numerous empty spaces (k) which
`were formerly misinterpreted as trabecular spaces. Wide-spacing fibers (1) are found near the
`trabecular space, and dense clumps of very fine filaments (m), possibly tropocollagen, are
`scattered throughout the wall. (x 12,400.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 10 of 21
`
`

`

`144
`
`CHAPTER FOUR
`
`or.
`
`Ia
`
`I
`
`. •
`
`r•
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`f,
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`•
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`A
`Figure 4-21. The inner wall of Schlemm's canal. A, The fibroblasts (a) resemble those
`of the cornea in their thickness and length. Long interconnecting cisternae of the rough-
`surfaced endoplasmic reticulum (b) and free ribosomes (c) are indicated. The mitochondria are
`small (d) and relatively sparse, and the nuclear chromatin is dispersed. The collagen fibrils (e)
`seen here measure less than 300 A. in diameter and are cut mostly in cross-section. Some of
`these fibrils are associated with masses of an electron-dense material (f). The endothelium of a
`trabecular space (g) is seen on the right. There is a layer of fibrillar material which varies in
`thickness adjacent to the endothelium, but it does not clearly represent a basement membrane.
`It contains clumps of wide-spacing fibers. (x 13,000.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 11 of 21
`
`

`

`LIMBUS
`
`145
`open and close intermittently, emptying their contents into the canal. The
`main function of the vacuoles would appear to to be in the active transport of
`large molecules such as proteins across the endothelium in order to circum-
`vent the barrier presented to these molecules by closure of the intercellular
`space by the zonulae occludentes. The smaller pinocytotic vesicles also
`found in the endothelium of Schlemm's canal probably work in conjunction
`with the large vacuoles in the active transport of substances.
`It is not clear whether a barrier to aqueous outflow is presented by the
`endothelium of the trabecular space nearest the juxtacanalicular tissue.
`Since this endothelium is not always continuous, aqueous humor may freely
`enter the connective tissue of the canal wall and then be incorporated into
`those vacuoles which are open. Finally, it should be emphasized that the
`greatest volume of aqueous humor diffuses passively through the wall of
`Schlemm's canal and that active transport may be needed only for large
`macromolecules and electrolytes.
`The External Collector Channels (Fig. 4-28). Twenty-five to 35
`veins emerge from the external wall of the canal of Schlemm and either join
`the deep scleral plexus directly or pass to the surface of the eye as aqueous
`veins. They are the principal route for the flow of aqueous humor from the
`canal of Schlemm into the episcleral veins. The channels are unevenly
`distributed around the circumference of the canal, being more numerous
`nasally than temporally, and are often connected to it in groups (Theobald,
`1934). Theobald showed in serial sections of human eyes that these channels
`connect with each other and with the deep scleral plexus of veins, but not
`with arterial channels. Ashton (1951), using neoprene injections, verified the
`existence of these channels in human eyes and verified their origin from the
`canal of Schlemm. In addition to those veins which arise from the canal of
`Schlemm and pass directly to the episcleral plexus, he found others that
`joined the deep scleral plexus of veins; from this plexus, collector channels
`then joined the episcleral vessels. Ashton also confirmed the absence of
`arterial connections to these veins even though the arteries were located
`close to, or even embedded in, the wall of Schlemm's canal. His prepara-
`tions also showed the presence of veins connecting the ciliary venous plexus
`with the deep scleral plexus.
`When studied with the electron microscope, the external collector
`vessels are seen to be lined by an endothelium similar to that along the outer
`wall of Schlemm's canal. The connective tissue of the wall of Schlemm's
`canal continues outward along the external collector channels as a very
`simple layer which may show an occasional muscle cell. The adventitia
`disappears from the walls of those vessels which join the deep scleral
`plexus.
`Internal Collector Channels (Fig. 4-29). Sondermann (1933) was the
`first to indicate that endothelial-lined canaliculi might connect the anterior
`
`Figure 4-21. Continued.
`B, Area similar to A to show the details of another fibroblast. The Golgi complex with its
`flattened cisternae (a) and associated vesicles (b) is prominent in the cytoplasm. Branching cis-
`ternae of rough-surfaced endoplasmic reticulum (c) also are prominent. Several vesicles are also
`observed, with an opened end toward the extracellular region (arrows). Free ribosomes (d) and
`cytoplasmic filaments (e) are indicated. (x 31,000.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 12 of 21
`
`

`

`146
`
`CHAPTER FOUR
`
`•if
`
`•
`
`•
`
`a.
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`Figure 4-22. See legend on opposite page.
`
`Petitioner - New World Medical
`Ex. 1010, p. 13 of 21
`
`

`

`THE LIMBUS
`
`147
`
`IJ
`
`-40;4
`
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`
`a
`
`•.X
`
`r
`
`a
`
`Figure 4-23. Schlemm's canal, external wall. The lumen of Schlemm's canal is at (a),
`while the junction of two endothelial cells is seen at (b). The granular, particulate nature of the
`material (c) is quite evident. Mature collagen fibrils are seen in cross-section (d,e), measuring
`1000 A. and 2000 A., respectively. A collagen fibril (arrow) is in contact with the endothelium, a
`relationship often seen in lymphatics. (X 67,500.)
`
`chamber to Schlemm's canal. Such channels were also described by Theo-
`bald (1934); Thomassen and Bakken (1951); Francois and associates (1955);
`Ashton (1956); Unger and Rohen (1959) and Iwamoto (1967 a, b). Other ob-
`servers have denied their existence, including Fortin (1942); Flocks (1956);
`Garron and Feeney (1959); Feeney and Wissig (1966); and Vegge (1967).
`Sondermann demonstrated at least five internal collector channels per exter-
`nal collector channel through serial sections and reconstructions of this region
`in a number of human eyes. Theobald observed that these channels are easy
`to overlook unless serial sections are made, since they are not evenly distrib-
`uted around the eye.
`Routine histologic sections of human eyes often show small endothelial-
`Text continued on page 153
`
`Figure 4-22. Schlemm's canal, external wall. The lumen of the canal is at (a). Pinocytotic
`vesicles (b) lie adjacent to both the outer and inner endothelial cell membrane. Two tight
`junctions or areas of membrane fusion are identified between two endothelial cells (arrows).
`The nuclei of two adjacent fibroblasts are shown at (c). Most of the mature collagen fibrils (d) are
`found a short distance from the canal wall; the cross-sectional diameter of the largest of these
`fibrils is approximately 600 A. A few collagen fibrils (e) appear within the fine particulate
`material (f) adjacent to the canal wall. This granular particulate material appears to be the
`ground substance of the canal wall. It is probably produced by both the fibroblasts and
`endothelial cells. (x 31,000.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 14 of 21
`
`

`

`148
`
`CHAPTER FOUR
`
`• •
`
`C
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`Voir
`
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`40 Alio,
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`• „.
`
`f, t
`
`Figure 4-24. Schlemm's canal, internal endothelium at the junction of two cells. There
`are numerous pincoytotic vesicles (a) which are filled with a finely granular material. These
`cells contain a large number of cytoplasmic fibrils (b). The intercellular space measures 200 A.
`except for a small area of contact. Small collagen fibrils (c) measuring approximately 200 A. are
`seen in longitudinal and cross-section. (x 88,000.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 15 of 21
`
`

`

`THE IAMBUS
`
`149
`
`•
`
`4.1
`
`Il
`
`Figure 4-25. Schlemm's canal, inner wall. Red blood cells and other cells are seen
`occasionally "in transit" between contiguous endothelial cells. A leukocyte (a) containing a
`bacterium (b) is mostly within the lumen of Schlemm's canal, but a small portion is in the canal
`wall. (x 32,000.)
`
`414 -74 1.:::*•
`
`1L,a4rwonsiaillt
`
`Petitioner - New World Medical
`Ex. 1010, p. 16 of 21
`
`

`

`150
`
`Yi
`
`b
`
`CHAPTER FOUR
`
`Sc
`
`a
`
`b
`
`:11
`
`ho%
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`row
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`t‘'
`
`Figure 4-26. A, Inner wall of Schlemm's canal (SC) showing a large endothelial vac-
`uole. Large vacuoles are found only in the inner wall of the canal. The giant vacuole (a) or
`vesicle measures 5µm. by 1.5 gm; its endothelial lining has several pinocytotic vesicles (b)
`opening into the lumen. (x 25,000.)
`B, Inner wall of Schlemm's canal. A giant vacuole (a) protrudes into the lumen of the
`canal (b). This vacuole measures 3 by 5µm. The internal canal wall has a number of fine collagen
`fibrils (c) measuring around 200 A. in diameter. Some fibroblasts are seen at the bottom of the
`figure. (x 14,000.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 17 of 21
`
`

`

`THE LIMBUS
`
`151
`
`•
`
`ti
`
`•
`
`II •
`
`4
`
`p
`
`ti
`
`C
`
`SC
`
`Figure 4-27. Inner wall of Schlemm's canal (SC). A giant vacuole (a) has an opening (b)
`which provides a clear passageway into the canal wall. Pinocytotic vesicles (c) are abundant.
`The arrow points to a tight junction between two endothelial cells. Pictures such as this suggest
`folds. When such large folds appear,
`that some "vacuoles" may be formed by large marginal
`however, they rarely extend freely into the canal lumen. (x 46,500.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 18 of 21
`
`

`

`152
`
`CHAPTER FOUR
`
`•
`
`*e t
`
`•
`
`•
`
`Figure 4-28. External collector channels and the deep scleral venous plexus. The exter-
`nal collector channels may join the deep scleral venous plexus or extend directly to the surface
`of the eye, where they join the episcleral venous plexus.
`A, An aqueous vein (a) can be differentiated from a deep scleral vein (b) by the absence
`of plasma in its lumen. The wall of the aqueous vein is thinner and less developed. (x 6200.)
`B, Higher magnification view of the wall of an aqueous vein. The endothelial cells are
`like those in other vessels and they are joined to each other by a zonula occludens (arrow).
`Occasional smooth muscle cells (a) may be seen in the wall of the aqueous vein. (x 13,000.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 19 of 21
`
`

`

`THE LIMBUS
`
`‘i‘
`
`' I
`
`• •
`
`4
`
`r i
`
`0 4 -
`
`S
`
`153
`
`V
`
`Sc
`
`ew
`
`IN
`
`Cm
`
`cst
`
`v►
`
`I
`
`Figure 4-29. Drawing of the canal of Schlemm, an internal collector channel and adja-
`cent tissues. The lumen of the canal (SC) is lined by endothelium (e). The endothelium of the
`inner wall is quite irregular, with many folds and outpouchings. Giant vacuoles (gv) are seen in
`the endothelial cells along the inner wall. The external wall of the canal (ew) is shown. The
`internal wall (iw) lies between the endothelium and the nearest trabecular space (ts). An
`internal collector channel (icc) arises near the posterior canal wall and extends into the
`trabecular meshwork, where it is lost. Like Schlemm's canal, it also is surrounded by a wall (a)
`which separates its lumen from the adjacent trabecular spaces. The corneoscleral trabecular
`sheets (cst) branch frequently, and their endothelial cells often form bridges between adjacent
`sheets.
`
`lined channels arising near the posterior part of Schlemm's canal and curv-
`ing forward into the trabecular meshwork. Some of these channels can be
`traced for a fairly long distance into the meshwork, but they almost always
`terminate in the inner trabecular meshwork. They have not been shown to
`traverse the entire corneoscleral meshwork into the anterior chamber.
`Iwamoto (1967a, b) employed light and electron microscopy to study
`these collectors and did find endothelial-lined channels that opened into
`Schlemm's canal from the deep intertrabecular spaces in both human adult
`and infant eyes. He followed some of these channels a considerable distance
`toward the anterior chamber; he failed, however, to demonstrate that they
`are uninterrupted channels from Schlemm's canal to the anterior chamber.
`We have studied these channels carefully in a number of eyes. The
`internal collector channels most often commence near the posterior part of
`Schlemm's canal as right-angle branches which are lined by endothelium
`
`Petitioner - New World Medical
`Ex. 1010, p. 20 of 21
`
`

`

`CHAPTER FOUR
`
`154
`and surrounded by adventitia. Shortly after emerging from the canal they
`turn to become parallel with it. The width of the collector channel at its
`opening into Schlemm's canal may be as large as 12 to 15µm. The diameter
`diminishes rapidly and soon is the caliber of the intertrabecular spaces. The
`internal collector channels are tortuous and branch frequently. We have
`been unable to establish a clear direct connection of the lumen of the
`collector with an intertrabecular space. We feel that the internal collectors
`are simply diverticulae of Schlemm's canal that serve to increase the total
`surface area of the inner wall. They are always surrounded by a wall which
`separates their endothelium from the nearest trabecular space. Those op-
`posed to the theory of the existence of through-and-through channels from
`the anterior chamber to the canal of Schlemm argue that the size and
`number of Sondermann's canals are too great to be consistent with known
`facts about the bulk flow of aqueous humor.
`
`Trabecular Meshwork (Fig. 4-16).
`The trabecular meshwork occupies most of the internal scleral sulcus.
`It has a somewhat triangular shape, its apex being near the end of Descemet's
`membrane and its base at the scleral spur. The anterior meshwork contains
`three to five layers and the posterior meshwork 15 to 20 layers. The larger
`number of posterior sheets is due to formation of new sheets from the wall of
`the internal scleral sulcus, and also from branching of pre-existing sheets as
`they extend posteriorly.
`Virchow (1910) was the first to divide the trabecular meshwork into
`scleral or corneoscleral and uveal portions. The former comprises the bulk of
`the meshwork, the latter forming only a thin, loose network on the inner
`surface of the corneoscleral meshwork.
`Corrteoscleral Meshwork (Figs. 4-30 to 4-37). The corneoscleral
`meshwork extends from the region of the end of Descemet's membrane and
`deep cornea to the sclera, scleral spur and ciliary body. Most of the mesh-
`work inserts into the sclera. Two to three sheets of the corneoscleral
`
`414,
`
`• 'X .
`
`-1"
`
`•
`
`•
`
`• 46411"..
`
`eftee
`
`.0. ID
`
`411.
`
`OW
`
`d Igo
`
`Figure 4-30. Corneoscleral meshwork, light micrograph. The sheets (a) and intertra-
`becular spaces (b) of the trabecular meshwork form an irregular mesh. The sheets show clumps
`and strands of pale material (c) and prominent clumps of dense material (d). The corneoscleral
`trabecular sheets vary in size, thickness and shape. Each sheet is surrounded by a continuous
`endothelium, and the sheets branch and merge with other sheets, causing the intertrabecular
`spaces to vary considerably in size and shape. Endothelial cells also branch and cross the
`intertrabecular spaces (e). (x 688.)
`
`Petitioner - New World Medical
`Ex. 1010, p. 21 of 21
`
`

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