The pathogenetic mechanism of progressive open angle glaucoma (POAG) is unproven. A significant decrease in the cellularity of the trabecular meshwork (TM) has been demonstrated in POAG specimens in comparison with age-matched normals. In its report """"""""Vision Research: A National Plan, 1983-1987,"""""""" stated: """"""""This finding may be significant in defining the etiology or natural history of glaucoma."""""""" We hypothesize that the common pathway necessary for the development of POAG is the loss of TM cells. Even if this hypothesis is wrong, a significant body of information can be obtained from understanding the effects of loss of TM cells on the outflow system the eye. The OBJECTIVE of this project is to use photochemical cytotoxicity which is made selective for (TM) cells to illuminate the role of the TM cell in the pathogenesis of progressive open angle glaucoma (POAG). To achieve this objective we SPECIFICALLY AIM to develop a method to injure or kill TM cells selectively. Selectively will be achieved by coupling a photosensitizer to a carrier (latex microspheres) which will be preferentially phagocytosed by TM cells. A second level of selectivity will be attained by spatially confining illumination to the TM using light emmitted from a dye laser. The photosensitizer will be activated only in the region of the TM, sparing surrounding tissues. Singlet oxygen production by the photosensitizer coupled microspheres will be assayed. The cytotoxic effects of the photosensitizer coupled carrier on TM cells will be evaluated first in TM cell culture, then following anterior chamber perfusion in cats and monkeys, in vivo. Scavengers and potentiators of activated oxygen species will be incubated with TM cells to determine which reactive species are responsible for cytotoxicity. Cellularity and morphologic changes of the TM and TM cells will be evaluated by light and electron microscopy. Once characterized in vivo, the effects of loss of TM cells selectively will be evaluated longitudinally with specific attention to: 1) changes in the morphology of the TM, 2) the effects on outflow facility and intraocular pressure, and 3) regenerative and reparative capacity of the TM using tritiated thymidine autoradiography. The methodology proposed in this study may provide a quantitative and inducible animal model for POAG.
| Latina, M A; Park, C (1995) Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. Exp Eye Res 60:359-71 |
