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Published October 2002 | public
Journal Article

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.

Additional Information

© 2002 Nature Publishing Group. Received 7 June; accepted 6 August 2002. Published online: 3 September 2002. We thank M. Danciger for help determining leucine/methionine polymorphism in Rpe65; D. Brunelle for help with graphics and manuscript preparation; F. Celestin of the SCOR in Ischemic Heart Disease Histology Core for assistance with histological sections; and D. Greuter, C. Imsand and G. Hoegger for technical assistance. Support for this research was provided by the US National Institutes of Health (J.L., M.I.S. and M.S.O.), Foundation Fighting Blindness (J.L.), Massachusetts Lions Eye Research Fund (an institutional grant to the Department of Ophthalmology, New England Medical Center) and Research to Prevent Blindness Special Scholar's Award (J.L.). C.E.R. received support from the Swiss National Science Foundation, German Research Council and Velux Foundation.

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