Light Induces Ultrastructural Changes in Rod Outer and Inner Segments, Including Autophagy, in a Transgenic @entity1238 @entity41812 XXXX Model of @entity6391 .

@entity2000 @entity50513 @entity1238 @entity41812 @entity16130 @entity6391 @entity291 @entity10627
Purpose: We previously reported a transgenic @entity1238 model of @entity6391 in which tadpoles express the @entity291 form of @entity41812 @entity10627 (b @entity41812 ) in rod photoreceptors. In this model, @entity2000 was dependent on light exposure. Here, we investigated ultrastructural changes that occurred in the rod photoreceptors of these retinas when exposed to light. Methods: Tadpoles expressing bP23H in rods were transferred from constant darkness to a 12-hour light:12-hour dark (12L:12D) regimen. For comparison, transgenic tadpoles expressing an inducible form of @entity50513 ( @entity50513 ) were reared in a 12L:12D regimen, and @entity2000 was induced by administration of the drug @entity16130 . Tadpoles were euthanized at various time points, and eyes were processed for confocal light and transmission electron microscopy. Results: We observed defects in outer and inner segments of rods expressing bP23H that were aggravated by light exposure. Rod outer segments exhibited vesiculations throughout and were rapidly phagocytosed by the retinal pigment epithelium. In rod inner segments, we observed autophagic compartments adjacent to the endoplasmic reticulum and extensive vesiculation at later time points. These defects were not found in rods expressing @entity50513 , which completely degenerated within 36 hours after drug administration. Conclusions: Our results indicate that ultrastructural defects in outer and inner segment membranes of bP23H expressing rods differ from those observed in drug-induced apoptosis. We suggest that light-induced @entity2000 caused by @entity41812 @entity10627 occurs via cell death with autophagy, which may represent an attempt to eliminate the mutant @entity10627 and/or damaged cellular compartments from the secretory pathway.
