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Tami P. Bogea, Beatrice T. Tam, Orson L. Moritz; Evidence of Type II Cell Death in P23H-Light Induced Retinal Degeneration in a Xenopus laevis Model of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2012;53(14):1138.
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Type II cell death, also described as cell death with autophagy, has been recently implicated in the regulation of photoreceptor degeneration in several mouse models . In the present study, we report the occurrence of type II cell death 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 transferred to a 12L: 12D regimen to induce retinal degeneration. They were euthanized at various time points. Transgenic tadpoles expressing an inducible form of caspase 9 (iCasp9) were reared similarly, and retinal degeneration was induced by administration of AP20187. Tadpole eyes were subsequently processed for high resolution electron microscopy according to standard procedures.
We observed defects in rod outer and inner segment membranes in tadpoles expressing bP23H, which were aggravated by exposure to cyclic light. Rod outer segments were shorter and exhibited vesiculations and altered disk morphology, and were rapidly phagocytosed by the retinal pigment epithelium. Phagocytosis was mostly complete by 36 hours. In rod inner segments, we observed autophagic compartments within the rough endoplasmic reticulum. In contrast, these defects were not observed in rod outer and inner segment membranes of tadpoles expressing iCasp9, where the photoreceptors completely degenerated within 24 hours.
Our results indicate the presence of ultrastructural defects in both the outer and inner segment membranes of bP23H expressing photoreceptors. These defects differed, however, from those observed in the drug induced rod apoptosis model, indicating that they are associated with the mechanism of light-induced retinal degeneration. We suggest that light-induced retinal degeneration occurs via type II cell death (cell death with autophagy), which is consistent with the instability of bP23H rhodopsin in outer segments and in the secretory pathwayupon light exposure.
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