Functional morphology of the trabecular meshwork in primate eyes
Introduction
The trabecular meshwork consists of a sponge-like, three-dimensionally arranged tissue expanded between cornea, scleral spur and uvea (Fig. 1). Aqueous humor has to pass the trabecular meshwork before entering the venous system via Schlemm's canal and collector channels. To maintain an intraocular pressure (IOP) of 17–19 mmHg against a venous pressure of 7–9 mmHg the tissues have to provide resistance to aqueous humor outflow. There has been a protracted debate as to the exact anatomical location of this resistance and to possible regulatory mechanism influencing outflow resistance and thereby IOP.
Theoretically resistance to aqueous flow could be influenced by changes in episcleral venous pressure. Recent immunohistochemical and scanning electronmicroscopic investigations of the episcleral venous system in various mammals including man revealed the presence of arteriovenous anastomoses in the episcleral venous plexus which derive from arterioles of the anterior ciliary arteries (Rohen and Funk, 1994a, Rohen and Funk, 1994b). The arterioles are densely innervated, indicating the presence of nervous mechanisms for regulating episcleral venous pressure and, correlated with that, intraocular pressure (Funk et al., 1996, Funk and Rohen, 1996).
However, the discussions about correlation between episcleral and intraocular pressure, particularly in cases of primary open angle glaucoma (POAG) are controversial (cf. Asamoto and Yablonski, 1996). Recently club- or bulb-shaped nerve endings (5–25 μm in diameter) have been identified in the scleral spur region (Tamm et al., 1994). These endings contain abundant neurofilaments, granular and agranular vesicles of different sizes and numerous mitochondria. They have intimate contact with the collagen fiber bundles of the scleral spur so that they could be considered to represent mechanoreceptive nerve endings for measuring stress or strain in the connective tissue elements of the scleral spur, induced by ciliary muscle contraction or changes in intraocular pressure. It is tempting to speculate that there might be a circuit between these receptors and the innervation of episcleral vessels. However, this topic will not be further discussed in the present article which will specifically concentrate on the role played by the trabecular meshwork for outflow resistance and glaucoma.
It is well established that about 50% of the resistance to aqueous outflow in the normal eye is located within the trabecular meshwork, in the extracellular matrix of the cribriform region near SC. The increased resistance to aqueous outflow found in POAG also is found within this region. The composition of the extracellular matrix, its changes in different types of glaucoma and its functional significance for the aqueous outflow resistance are not completely understood. We have used three different approaches to analyse these problems: (1) experimental studies; (2) morphological studies in human donor eyes; and (3) testing trabecular cells in vitro.
In human eyes with a well developed accommodation system the trabecular meshwork shows considerable morphological differences from that seen in other mammals in which a true accommodation system is not developed. In bovine, porcine and rabbit eyes, often used in eye research, a true canal of Schlemm does not exist. There are instead numerous capillary loops extending into a reticular meshwork. In various mammalian species and many subprimates a clear differentiation into a lamellated corneoscleral and a nonlamellated subendothelial region does not exist and a reticular meshwork is developed instead. Most often the chamber angle shows a well-developed pectinate ligament with large spaces of Fontana. Posteriorly the relatively small ciliary muscle is connected to a loosely arranged connective tissue containing numerous myofibroblast-like cells. These cells are in contact with the capillary loops and presumably prevent their collaps (Flügel et al., 1991) (for review see Rohen, 1964; Tripathi, 1974). It is not yet known whether the biological functions of cells derived from the reticular meshwork are the same as those of trabecular cells of primate eyes, especially if these cells are studied under tissue culture conditions. We will therefore concentrate mainly on results obtained from the trabecular meshwork of human or monkey eyes or from cell- or tissue-cultures derived from human or monkey trabecular cells exclusively.
Section snippets
The corneoscleral meshwork
From the functional point of view, the trabecular meshwork consists of two main portions: (a) the inner lamellated uveal and corneoscleral portion, and (b) the non-lamellated cribriform layer or juxtacanalicular meshwork forming part of the inner wall of Schlemm's canal (for review see Lütjen-Drecoll and Rohen, 1992, Lütjen-Drecoll and Rohen, 1994, Lütjen-Drecoll and Rohen, 1996) (Fig. 1). The lamellated meshwork can be further divided into the innermost uveal lamellae expanded between cornea
Resistance to aqueous humor outflow
From experimental studies in enucleated human eyes Grant (1963)concluded, that about 75% of the resistance is located internally to SC within the trabecular meshwork. Recent experimental studies in monkey eyes revealed that nearly 90% of the resistance is located in the subendothelial region of SC (Mäepea and Bill, 1992).
The structural components mainly responsible for this resistance are still not completely known. In a combined physiologic and morphometric study on thailand stumptailed monkey
Influence of ciliary muscle contraction
In primate eyes with well developed accommodation, ciliary muscle contraction can expand the trabecular meshwork thereby enhancing the filtration area of the inner wall of SC so that outflow resistance is reduced (Rohen et al., 1967). Pilocarpine, which induces ciliary muscle contraction, has been one of the mainstays in glaucoma therapy for over 100 years. Rohen and Unger (1959)have investigated the anterior insertion of the ciliary muscle in serial tangential sections and found, that the
Myofibroblast-like cells
Within the trabecular meshwork as well as in the scleral spur, cells were found which stained with antibodies against smooth muscle (sm) α-actin (Fig. 10), myosin but not for desmin (Ringvold, 1978; Flügel et al., 1991; DeKater et al., 1992). Ultrastructurally these cells resemble myofibroblasts. In the trabecular meshwork of younger human eyes, myofibroblast-like cells are randomly distributed throughout the entire meshwork (Flügel et al., 1992b). With increasing age the number is markedly
Primary open angle glaucoma (POAG)
In most eyes with primary open angle glaucoma intraocular pressure (IOP) is increased, and the optic nerve head shows characteristic cupping correlated with visual field-defects. The resistance to aqueous outflow is significantly increased. Pathogenetic factors causative for these changes are still unknown. Electronmicroscopically, in trabeculectomy specimens mostly derived from advanced stages of the disease, characteristic changes of the extracellular matrix have been described by several
Tissue culture studies
Because of the lack of suitable animal models, studies about the biological reactivities of trabecular cells, particularly with respect to the pathogenesis of glaucoma, were preferentially performed on cells under tissue culture conditions. The first successful studies on monolayer cultures of trabecular cells derived from human or monkey eyes were described by Rohen et al. (1976), Rohen et al. (1982)) and Polansky et al. (1979). In the last two decades a great number of tissue culture studies
Future directions
In the past the morphology of the trabecular meshwork has mostly been described under mechanical aspects. Future research has to concentrate more on the biology of trabecular cells and trabecular meshwork reactions. It is well established that the trabecular meshwork is to large extent site of aqueous outflow resistance and that the extracellular material located within the cribriform layer is mainly responsible for that resistance. We have described the composition of the extracellular
Acknowledgements
The study summarized in this article is supported by SFB 539 B I/l, Academy of Science and Literature in Mainz, Biomed P1 96 1593.
References (135)
- et al.
Dexamethasone treatment decreases hyaluronan-formation by primate trabecular meshwork cells in vitro
Exp. Eye Res.
(1997) - et al.
Different cell populations in bovine trabecular meshwork: an ultrastructural and immunocytochemical study
Exp. Eye Res.
(1991) - et al.
Age-related changes of sulfated proteoglycans in the normal human trabecular meshwork
Exp. Eye Res.
(1992) - et al.
Platelet Aggregation on the Endothelium of Schlemm's Canal
Experimental Eye Res.
(1994) - et al.
Effect of transforming growth factor-b on collagen type VI expression in human dermal fibroblasts
FEBS
(1992) Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix
J. Biol. Chem.
(1986)- et al.
The effect of organ culture on human trabecular meshwork
Exp. Eye Res.
(1989) - et al.
Immunomicroscopical study of type VI collagen in the trabecular meshwork of normal and glaucomatous eyes
Exp. Eye Res.
(1989) - et al.
Visualization of hyaluronic acid in the anterior segment of rabbit and monkey eyes
Exp. Eye Res.
(1990) - et al.
Quantitative analysis of `plaque material' in the inner- and outer wall of Schlemm's canal in normal- and glaucomatous eyes
Exp. Eye Res.
(1986)