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A photic visual cycle of rhodopsin regeneration is dependent on Rgr

Nature Genetics volume 28, pages 256–260 (2001)Cite this article

Abstract

During visual excitation, rhodopsin undergoes photoactivation and bleaches to opsin and all-trans-retinal1,2. To regenerate rhodopsin and maintain normal visual sensitivity, the all-trans isomer must be metabolized and reisomerized to produce the chromophore 11-cis-retinal in biochemical steps that constitute the visual cycle and involve the retinal pigment epithelium (RPE; refs. 3–8). A key step in the visual cycle is isomerization of an all-trans retinoid to 11-cis-retinol in the RPE (refs. 9–11). It could be that the retinochrome-like opsins, peropsin, or the retinal G protein-coupled receptor (RGR) opsin12–16 are isomerases in the RPE. In contrast to visual pigments, RGR is bound predominantly to endogenous all-trans-retinal, and irradiation of RGR in vitro results in stereospecific conversion of the bound all-trans isomer to 11-cis-retinal17. Here we show that RGR is involved in the formation of 11-cis-retinal in mice and functions in a light-dependent pathway of the rod visual cycle. Mutations in the human gene encoding RGR are associated with retinitis pigmentosa18.

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Figure 1: Targeted disruption of mouse Rgr.
Figure 2: Total retinal and rhodopsin in Rgr+/+, Rgr+/− and Rgr−/− mice.
Figure 3: Effect of ambient light of various intensities on the amount of total retinal and rhodopsin in Rgr+/+ and Rgr−/− mice.
Figure 4: Steady-state accumulation of all-trans-retinyl ester in light-adapted Rgr+/+ and Rgr−/− mice.
Figure 5: ERG responses of Rgr+/+ and Rgr−/− mice after exposure to constant illumination.
Figure 6: Regeneration of rhodopsin in the dark after brief irradiation of Rgr+/+ and Rgr−/− mice.

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Acknowledgements

We thank A. Mendez for advice about ES cell culture, A. Nagy for the gift of R1 ES cells and L. LaBree for work on statistical analysis of data. This work was supported by grants from the Hoover Foundation and the U.S. Public Health Service (EY08364 and EY03040).

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Authors and Affiliations

  1. Department of Ophthalmology, University of Southern California, Los Angeles, 90033, California, USA

    Pu Chen, Lawrence Rife, Gretchen B. Van Boemel & Henry K.W. Fong

  2. Department of Microbiology, University of Southern California, Los Angeles, 90033, California, USA

    Wenshan Hao, Mao Yang & Henry K.W. Fong

  3. Department of Cell and Neurobiology, University of Southern California, Los Angeles, 90033, California, USA

    Jeannie Chen

  4. Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, 90033, California, USA

    Lanyin Wu

  5. Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, 90033, California, USA

    Pu Chen

  6. Doheny Eye Institute, Los Angeles, 90033, California, USA

    Xiao Peng Wang, Daiwei Shen, Thomas Ogden, Gretchen B. Van Boemel & Henry K.W. Fong

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  1. Pu Chen
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Correspondence to Henry K.W. Fong.

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Chen, P., Hao, W., Rife, L. et al. A photic visual cycle of rhodopsin regeneration is dependent on Rgr. Nat Genet 28, 256–260 (2001). https://doi.org/10.1038/90089

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