Evidence for two apoptotic pathways in light-induced retinal degeneration

Wenshan Hao, Andreas Wenzel, Martin S Obin, Ching-Kang Chen, Elliott Brill, Nataliia V Krasnoperova, Pamela Eversole-Cire, Yelena Kleyner, Allen Taylor, Melvin I Simon, Christian Grimm, Charlotte E Remé, Janis Lem


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.