Evidence for two apoptotic pathways in light-induced retinal degeneration.
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.
Hao
Wenshan
W
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Wenzel
Andreas
A
Obin
Martin S
MS
Chen
Ching-Kang
CK
Brill
Elliott
E
Krasnoperova
Nataliia V
NV
Eversole-Cire
Pamela
P
Kleyner
Yelena
Y
Taylor
Allen
A
Simon
Melvin I
MI
Grimm
Christian
C
Remé
Charlotte E
CE
Lem
Janis
J
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
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