Photoreceptor Death, Trophic Factor Expression, Retinal Oxygen Status, and Photoreceptor Function in the P23H Rat

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Abstract
Purpose. To relate the oxygen environment of the retina to photoreceptor stability, protection, and function in the P23H rat. methods. Heterozygote P23H-3 (Line 3) rats were studied. Photoreceptor death rates were assessed with the TUNEL technique for detection of fragmenting DNA, in a developmental series from postnatal day (P)16 to P105 (adult). In adult retinas, trophic factor status was assessed with immunohistochemistry, intraretinal oxygen environment with O2-sensing electrodes, and photoreceptor function by the flash-evoked, dark-adapted electroretinogram (ERG), recorded in anesthetized animals. results. Photoreceptor death begins by P16; peaks at P25, when the frequency of TUNEL+ profiles exceeds 70/mm of retina; and then declines to low (2 tension and uptake are relatively normal in the inner retina, but uptake is considerably reduced, and O2 tension is significantly raised in the outer retina. Surviving photoreceptors generate an a-wave with normal peak latency but sharply reduced amplitude. conclusions. Excess photoreceptor degeneration in the P23H-3 retina begins just after eye opening, peaks in early postnatal life, and then slows, but persists into adulthood. In the adult retina, surviving photoreceptors operate in an environment that is chronically hyperoxic (and therefore toxic) and in which protective factors (CNTF, FGF-2) are chronically upregulated. The net result, slow degeneration and degraded function in an environment that is both toxic and protective, may be representative of adult photoreceptor status in a number of human retinal degenerations. Hyperoxia-induced photoreceptor death may be a self-reinforcing factor that increases oxidative stress in surviving photoreceptors.

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