Primary open angle glaucoma is almost certainly a result of changes in the metabolism of trabecular meshwork (TM). This was recognized by the Glaucoma Panel in its 1983 report to the National Advisory Eye Council when it stated as an objective """"""""To define the biology and pharmacology of the aqueous humor outflow pathways at the cellular, tissue, and organ levels -----"""""""". This proposal is centered in this set of objectives. The pathogenetic mechanism of glaucoma is still unknown. However, we will take as our working hypothesis that glaucoma is the result of failure to cope with chronic exposure to oxidative insult, in particular the hydrogen peroxide present in human aqueous humor. Even if wrong, the focused effort will produce a coherent body of useful information on the biology of TM. The use of excised calf TM as a model system will continue to be the mainstay of our work. An important new development is our ability to produce isolated cell suspensions of calf TM. Experience with other tissues has shown that there are great advantages in such a preparation. The difficulty of working with excised human TM and the uncertainty of the supply necessitate a new approach. We propose to develop methods for perfusing preparations of isolated TM mounted on corneoscleral buttons, four from each eye. The enzymes of energy metabolism, etc. will continue to be studied, but the primary emphasis has shifted to enzymes participating in the defense of TM against oxidative damage. Potential targets of oxidative damage will also be studied, such as the membrane ATPases, hormone receptors, and membrane lipid. An attempt will be made to develop an oxidative damage model of glaucoma in rabbits by manipulations designed to raise aqueous H2O2 levels.
| Nguyen, K P; Chung, M L; Anderson, P J et al. (1988) Hydrogen peroxide removal by the calf aqueous outflow pathway. Invest Ophthalmol Vis Sci 29:976-81 |
| Lee, D A; Flores, R A; Anderson, P J et al. (1987) Glaucoma filtration surgery in rabbits using bioerodible polymers and 5-fluorouracil. Ophthalmology 94:1523-30 |
| Nguyen, K; Lee, D A; Anderson, P J et al. (1986) Glucose 6-phosphate dehydrogenase of calf trabecular meshwork. Invest Ophthalmol Vis Sci 27:992-7 |
| Nguyen, K P; Weiss, H; Karageuzian, L N et al. (1985) Glutathione reductase of calf trabecular meshwork. Invest Ophthalmol Vis Sci 26:887-90 |
| Freedman, S F; Anderson, P J; Epstein, D L (1985) Superoxide dismutase and catalase of calf trabecular meshwork. Invest Ophthalmol Vis Sci 26:1330-5 |
