LIGHT-INDUCED CELL-DEATH OF RETINAL PHOTORECEPTORS IN THE ABSENCE OF P53

PURPOSE. Cell death by apoptosis is essential for normal development a nd tissue homeostasis, and it is involved also in a variety of patholo gic processes. Apoptosis is the final common pathway of photoreceptor cell death in retinal dystrophies and degeneration So far, little is k nown about genes regulating apoptosis in the retina. The tumor-suppres sor gene product p53 is a potent regulator of apoptosis in numerous sy stems. However, p53-independent apoptotic pathways also have been desc ribed. In this study the authors investigated the role of p53 in the l ight-induced apoptosis of retinal photoreceptors using mice lacking p5 3. METHODS. Free-moving p53(-/-) and p53(+/+) mice were dark adapted a nd were exposed to 8,500 or 15,000 lux of diffuse, cool, white fluores cent Light for 2 hours. Animals were killed before and immediately aft er light exposure or at 12 hours in darkness after light exposure. Eye s were enucleated and processed for light and electron microscopy and histochemistry (TdT-dUTP terminal nick-end labeling method). Isolated retinas were subjected to the extraction of total retinal DNA. Electro retinogram (ERG) recordings were performed at all time points. RESULTS . Morphologic, biochemical, histochemical, and ERG analysis showed tha t the retinas of untreated p53(-/-) mice and wild-type control mice we re structurally and functionally indistinguishable. After exposure to diffuse white fluorescent light, light-induced photoreceptor cell deat h was analyzed and was found to be the same in both groups of mice. CO NCLUSIONS. These data suggest that light-induced apoptosis of photorec eptors is independent of functional p53.