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Abstract
PURPOSE: To investigate the developing retina of normal and rd/rd mice to establish if the inherited defect in the retinal degeneration (rd) gene, encoding the beta subunit of the cascade phosphodiesterase, is associated with rd photoreceptor degeneration by apoptosis. METHODS: DNA content of developing normal and rd/rd retinas was measured spectrophotometrically and analyzed for differential loss during the course of photoreceptor degeneration. Degenerating rd photoreceptors were evaluated by electron microscopy for cytoplasmic features and chromosomal condensation. DNA fragmentation was analyzed by agarose gel electrophoresis at daily intervals during the developmental period in which rd/rd cell death occurs. RESULTS: DNA loss from developing rd/rd retinas is maximal between 10 and 15 postnatal days. Photoreceptor cells die individually throughout the postnatal period of degeneration, with pycnotic nuclei dispersed among morphologically normal rd photoreceptors. DNA fragmentation into 200 base pair multiples occurs maximally in rd/rd retinas between 10 and 15 postnatal days. CONCLUSION: Photoreceptor cell death in developing rd/rd retinas occurs by a mechanism that links a defect in the phototransduction cascade with a program for cell death, called apoptosis.