title: Evidence for two apoptotic pathways in light-induced retinal degeneration.
abstract: Excessive phototransduction signaling is thought to be involved in light-induced and inherited retinal degeneration. Using knockout mice with defects in rhodopsin shut-off and transducin signaling, we show that two different pathways of photoreceptor-cell apoptosis are induced by light. Bright light induces apoptosis that is independent of transducin and accompanied by induction of the transcription factor AP-1. By contrast, low light induces an apoptotic pathway that requires transducin. We also provide evidence that additional genetic factors regulate sensitivity to light-induced damage. Our use of defined mouse mutants resolves some of the complexity underlying the mechanisms that regulate susceptibility to retinal degeneration.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Wenshan
authors.initials: W
authors.lastname: Hao
authors.forename: Andreas
authors.initials: A
authors.lastname: Wenzel
authors.forename: Martin S
authors.initials: MS
authors.lastname: Obin
authors.forename: Ching-Kang
authors.initials: CK
authors.lastname: Chen
authors.forename: Elliott
authors.initials: E
authors.lastname: Brill
authors.forename: Nataliia V
authors.initials: NV
authors.lastname: Krasnoperova
authors.forename: Pamela
authors.initials: P
authors.lastname: Eversole-Cire
authors.forename: Yelena
authors.initials: Y
authors.lastname: Kleyner
authors.forename: Allen
authors.initials: A
authors.lastname: Taylor
authors.forename: Melvin I
authors.initials: MI
authors.lastname: Simon
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Remé
authors.forename: Janis
authors.initials: J
authors.lastname: Lem
mesh_terms: D000818:Animals; D017209:Apoptosis; D019393:Arrestin / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins; D003907:Dexamethasone / Q000378:metabolism; D005136:Eye Proteins; D051606:G-Protein-Coupled Receptor Kinase 1; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects*; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015293:Transducin / Q000378:metabolism; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D019393:Arrestin; D002352:Carrier Proteins; D003907:Dexamethasone; D005136:Eye Proteins; D051606:G-Protein-Coupled Receptor Kinase 1; D011494:Protein Kinases; D011506:Proteins; D012243:Rhodopsin; D018808:Transcription Factor AP-1; D015293:Transducin; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C496762:Grk1 protein, mouse