title: Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration.
abstract: Light-induced apoptosis of photoreceptors represents an animal model for retinal degeneration. Major human diseases that affect vision, such as age-related macular degeneration (AMD) and some forms of retinitis pigmentosa (RP), may be promoted by light. The receptor mediating light damage, however, has not yet been conclusively identified; candidate molecules include prostaglandin synthase, cytochrome oxidase, rhodopsin, and opsins of the cones and the retinal pigment epithelium (PE). We exposed to bright light two groups of genetically altered mice that lack the visual pigment rhodopsin (Rpe65-/- and Rho-/-). The gene Rpe65 is specifically expressed in the PE and essential for the re-isomerization of all-trans retinol in the visual cycle and thus for the regeneration of rhodopsin after bleaching. Rho-/- mice do not express the apoprotein opsin in photoreceptors, which, consequently, do not contain rhodopsin. We show that photoreceptors lacking rhodopsin in these mice are completely protected against light-induced apoptosis. The transcription factor AP-1, a central element in the apoptotic response to light, is not activated in the absence of rhodopsin, indicating that rhodopsin is essential for the generation or transduction of the intracellular death signal induced by light.
authors.affiliation: Laboratory of Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. cgrimm@opht.unizh.ch
authors.forename: C
authors.initials: C
authors.lastname: Grimm
authors.forename: A
authors.initials: A
authors.lastname: Wenzel
authors.forename: F
authors.initials: F
authors.lastname: Hafezi
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.forename: T M
authors.initials: TM
authors.lastname: Redmond
authors.forename: C E
authors.initials: CE
authors.lastname: Remé
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002352:Carrier Proteins; D005136:Eye Proteins; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000528:radiation effects; D010857:Pigment Epithelium of Eye / Q000528:radiation effects*; D011506:Proteins / Q000235:genetics*; D012162:Retinal Degeneration / Q000209:etiology* / Q000473:pathology; D012243:Rhodopsin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000528:radiation effects; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D012243:Rhodopsin; D018808:Transcription Factor AP-1; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase