MULLER AND RPE CELL RESPONSE TO PHOTORECEPTOR CELL DEGENERATION IN AGING FISCHER RATS

With increasing age, retinas of male Fischer rats gradually lose photo receptor cells beginning at the ora serrata and extending to the centr al retina resulting in a pronounced peripheral retinopathy. In this st udy, we used immunocytochemical methods for glial fibrillary acidic pr otein (GFAP) and carbonic anhydrase II (CA II) to study the Muller cel l response to age-related photoreceptor cell degeneration in the super ior retina. Retinas of Fischer rats were also examined by electron mic roscopy to investigate retinal pigment epithelial (RPE) cell and Bruch 's membrane structural changes with advancing age. Our study showed ex tensive photoreceptor cell loss in the region of the ora serrata begin ning by 16 months, while few photoreceptor cells were found at 23 mont hs. Neovascularization also occurred in the area of the peripheral ret inopathy at the level of the RPE cells as determined by electron micro scopy; as well as a thickening of Bruch's membrane with initial signs of small breaks. Dense areas of GFAP-immunostaining of Muller cell pro cesses were found in the superior peripheral retina of 16-30 month-old rats where photoreceptor cells were degenerating. After 21 months, Mu ller cell processes extended into the subretinal space. However, in th e central retina, where the photoreceptor cell population was more sta ble, GFAP-immunolabelled Muller cells were not detected. Immunoblots o f retinal homogenates confirmed elevated GFAP levels at 18-30 months w hen compared to homogenates from retinas of 6-month-old Fischer rats. During photoreceptor cell degeneration, Muller cell processes were als o prominently immunostained for CA II, which were seen to occupy the s ubretinal space at 18-30 months. Our results suggest that Muller cells respond to the age-related peripheral retinopathy in Fischer rats by increasing GFAP content and growth of their processes into the subreti nal space to form a glial scar, but only in the area of severe photore ceptor cell loss. In addition, RPE and Bruch's membrane of aged retina s exhibit typical early age-related changes as also reported for aged human eyes. (C) 1996 Academic Press Limited