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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis*
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Arrestin / genetics
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Arrestin / metabolism
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Carrier Proteins
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Dexamethasone / metabolism
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Eye Proteins*
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G-Protein-Coupled Receptor Kinase 1
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Light / adverse effects*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mutation
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Photoreceptor Cells, Vertebrate / physiology
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Proteins / metabolism
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Retina / metabolism
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Retina / physiopathology
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Retina / radiation effects*
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Rhodopsin / metabolism
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Signal Transduction
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Transcription Factor AP-1 / antagonists & inhibitors
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Transcription Factor AP-1 / metabolism
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Transducin / metabolism
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cis-trans-Isomerases
Substances
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Arrestin
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Carrier Proteins
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Eye Proteins
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Proteins
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Transcription Factor AP-1
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Dexamethasone
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Rhodopsin
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Protein Kinases
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G-Protein-Coupled Receptor Kinase 1
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Grk1 protein, mouse
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retinoid isomerohydrolase
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Transducin
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cis-trans-Isomerases