The basic mechanisms underlying the regulation of the outflow of aqueous humor from the eye remain unknown, yet increased knowledge of these mechanisms could lead to better understanding of the pathogenesis of glaucoma or possibly its prevention. We propose an intensive investigation of certain of the properties of the trabecular meshwork cells, properties which are intimately involved in aqueous outflow and which could be highly influential in control of intraocular pressure. Experimental and clinical studies have shown that the trabecular meshwork is a dynamic tissue whose cells synthesize extracellular matrix components, phagocytose particulate materials entering the aqueous humor, and help to organize and maintain the structure of the outflow system. These highly differentiated cellular functions are acquired relatively late in the development of the eye, yet are retained by cultured trabecular cells. This study will use trabecular meshwork tissue and cultures of trabecular meshwork cells to do the following: (1) Identify and characterize the proteoglycans present in trabecular meshwork and those synthesized by trabecular cells; (2) Determine the influence of extracellular matrix components on proteoglycan biosynthesis using biochemical, ultrastructural and autoradiographic techniques; (3) identify and begin to characterize the phagocytic mechanisms of trabecular cells - both receptor mediated mechanisms (Fc, C3 and zymosan receptors) and non-specific mechanisms (latex particles) will be studied; and (4) characterize the distribution of specific cytoskeletal proteins in trabecular meshwork cells both in vitro and in vivo (in various regions of the trabecular meshwork), using immunofluorescence and immunoelectron microscopy. Actin filaments, microtubules and intermediate filaments will be studied as will the actin filament cross linking proteins myosin and alpha-actinin, and the microfilament attachment proteins spectrin and vinculin. The reorganization of cytoskeletal proteins during phagocytosis and the modulation of cytoskeletal organization by extracellular matrix and anti-glaucoma drugs will also be studied.
| Sherwood, M E; Richardson, T M (1988) Phagocytosis by trabecular meshwork cells: sequence of events in cats and monkeys. Exp Eye Res 46:881-95 |
| Higginbotham, E J; Richardson, T M (1987) Effect of vitamin A on glycoconjugate: synthesis in the trabecular meshwork. A preliminary report. Exp Eye Res 44:697-702 |
| Crean, E V; Tyson, S L; Richardson, T M (1986) Factors influencing glycosaminoglycan synthesis by calf trabecular meshwork cell cultures. Exp Eye Res 43:365-74 |
| Ethier, C R; Kamm, R D; Palaszewski, B A et al. (1986) Calculations of flow resistance in the juxtacanalicular meshwork. Invest Ophthalmol Vis Sci 27:1741-50 |
| Crean, E V; Sherwood, M E; Casey, R et al. (1986) Establishment of calf trabecular meshwork cell cultures. Exp Eye Res 43:503-17 |
| Richardson, T M; Brown, S V; Thomas, J V et al. (1985) Shock-wave effect on anterior segment structures following experimental neodymium:YAG laser iridectomy. Ophthalmology 92:1387-95 |
