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Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration

Nature Geneticsvolume 25pages6366 (2000) | Download Citation

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Abstract

Light-induced apoptosis of photoreceptors represents an animal model for retinal degeneration1. Major human diseases that affect vision, such as age-related macular degeneration (AMD) and some forms of retinitis pigmentosa (RP), may be promoted by light2,3,4,5,6,7. The receptor mediating light damage, however, has not yet been conclusively identified; candidate molecules include prostaglandin synthase8, cytochrome oxidase9, rhodopsin10, and opsins of the cones and the retinal pigment epithelium11 (PE). We exposed to bright light two groups of genetically altered mice that lack the visual pigment rhodopsin (Rpe65−/− and Rho−/−). The gene Rpe65 is specifically expressed in the PE and essential for the re-isomerization of all-trans retinol in the visual cycle and thus for the regeneration of rhodopsin after bleaching12. Rho−/− mice do not express the apoprotein opsin in photoreceptors, which, consequently, do not contain rhodopsin13. We show that photoreceptors lacking rhodopsin in these mice are completely protected against light-induced apoptosis. The transcription factor AP-1, a central element in the apoptotic response to light14,15, is not activated in the absence of rhodopsin, indicating that rhodopsin is essential for the generation or transduction of the intracellular death signal induced by light.

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Acknowledgements

We thank T.P. Williams for critical comments on the manuscript; P. Humphries and M. Seeliger for providing Rho−/− mice; and K. Munz, C. Imsand, G. Hoegger and D. Greuter for technical assistance.This work was supported by the Swiss National Science Foundation and the E&B Grimmke Foundation.

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Affiliations

  1. Department of Ophthalmology, Laboratory of Retinal Cell Biology, University Hospital Zurich, Zurich, Switzerland

    • Christian Grimm
    • , Andreas Wenzel
    • , Farhad Hafezi
    •  & Charlotte E. Remé
  2. Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, Maryland, USA

    • Shirley Yu
    •  & T. Michael Redmond

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Correspondence to Christian Grimm.

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https://doi.org/10.1038/75614

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