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Tami Bogea, Beatrice Tam, Orson Moritz; P23H-Light Induced Retinal Degeneration occurs via cell death with autophagy in a Xenopus laevis Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1775. doi: https://doi.org/.
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Autophagy has been recently implicated in the regulation of photoreceptor degeneration in several vertebrate models. In this study, we report the presence of cell death with autophagy in a light induced model of retinal degeneration where Xenopus laevis tadpoles express a bovine form of the rhodopsin mutant P23H (bP23H).
Transgenic tadpoles expressing bP23H were reared in the dark for 5 days and subsequently transferred to a 12L: 12D regimen to induce retinal degeneration. Tadpole eyes were subsequently processed for quantitative dot blots, immunohistochemistry and transmission electron microscopy according to standard procedures.
We observed a significant decrease in the amount of total rhodopsin in tadpoles expressing bP23H. We also observed defects in rod outer and inner segment membranes in tadpoles expressing bP23H. Rod outer segments were shorter and exhibited vesiculations and altered disk morphology, and were rapidly phagocytosed by the retinal pigment epithelium. In rod inner segments, we observed increased numbers of autophagic compartments within the rough endoplasmic reticulum in tadpoles expressing bP23H. In contrast, these defects were not observed in rod outer and inner segment membranes of wild type tadpoles.
Our results indicate the presence of defects in both outer and inner segment membranes of bP23H expressing photoreceptors. These defects were not observed in wild type tadpoles, suggesting that they are associated with the mechanisms of P23H- light induced retinal degeneration. We hypothesize that autophagy represents an attempt to eliminate damaged cellular compartments and mutant P23H rhodopsin from the secretory pathway.
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