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Article
Nature Genetics  32, 254 - 260 (2002)
Published online: 3 September 2002; | doi:10.1038/ng984

Evidence for two apoptotic pathways in light-induced retinal degeneration

Wenshan Hao1, 6, 7, Andreas Wenzel2, 7, Martin S. Obin3, 7, Ching-Kang Chen1, 6, 7, Elliott Brill4, Nataliia V. Krasnoperova4, Pamela Eversole-Cire1, Yelena Kleyner5, Allen Taylor3, Melvin I. Simon1, Christian Grimm2, Charlotte E. Remé2, 8 & Janis Lem4, 5, 8

1  Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.

2  Laboratory of Retinal Cell Biology, University Hospital Zurich, CH-8091 Zurich, Switzerland.

3  Nutrition and Vision Research Laboratory, JMUSDA-HNRCA at Tufts University, Boston, Massachusetts 02111, USA.

4  Department of Ophthalmology and Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.

5  Program in Genetics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

6  Department of Oncology, Wyeth Research, Pearl River, New York 10965, USA (W.H.); Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah 84112, USA (C.-K.C.).

7  These authors contributed equally to this work.

8  These authors contributed equally to this work.

Correspondence should be addressed to Janis Lem Jlem@lifespan.org
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.

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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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