Abstract

Vertebrate RPE and Muller cells contain a cytoplasmic visual pigment homolog termed RGR (for RPE retinal G protein-coupled receptor) which binds retinoid and shares sequence similarity with retinochrome, a photoisomerase in squid photoreceptors. This application hypothesizes that RGR may function as a retinal isomerase in the vertebrate visual cycle, be involved in a primitive form of phototransduction, play a role in circadian rhythm, or act as a sensor of free retinaldehyde. To test these hypotheses, research will investigate RGR ligand- and protein-binding properties and analyze the phenotype resulting from mutation of the RGR gene in a RGR-less mouse model system. The endogenous chromophore of bovine RGR will be identified and photoisomerization of retinal bound to natural and recombinant RGR will be investigated. A splice variant of the human RGR gene termed RGR-d has been identified in which the predicted sixth transmembrane domain is deleted. To investigate the possibility that RGR-d is involved in diseases of the retina such as age-related macular degeneration (AMD), studies will characterize human RGR-d retinaldehyde-binding properties, subcellular localization and other possible altered properties.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008364-10
Application #
6138154
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
1990-08-01
Project End
2001-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
10
Fiscal Year
2000
Total Cost
$302,436
Indirect Cost

  Institution

Name
Doheny Eye Institute
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90033

  Publications

Zhang, Zhaoxia; Fong, Henry K W (2018) Coexpression of nonvisual opsin, retinal G protein-coupled receptor, and visual pigments in human and bovine cone photoreceptors. Mol Vis 24:434-442
Kochounian, Harold; Zhang, Zhaoxia; Spee, Christine et al. (2016) Targeting of exon VI-skipping human RGR-opsin to the plasma membrane of pigment epithelium and co-localization with terminal complement complex C5b-9. Mol Vis 22:213-23
Kochounian, Harold; Johnson, Lincoln V; Fong, Henry K W (2009) Accumulation of extracellular RGR-d in Bruch's membrane and close association with drusen at intercapillary regions. Exp Eye Res 88:1129-36
Lin, Meng-Yin; Kochounian, Harold; Moore, Roger E et al. (2007) Deposition of exon-skipping splice isoform of human retinal G protein-coupled receptor from retinal pigment epithelium into Bruch's membrane. Mol Vis 13:1203-14
Fong, Henry K W; Lin, Meng-Yin; Pandey, Sujay (2006) Exon-skipping variant of RGR opsin in human retina and pigment epithelium. Exp Eye Res 83:133-40
Yang, Mao; Fong, Henry K W (2002) Synthesis of the all-trans-retinal chromophore of retinal G protein-coupled receptor opsin in cultured pigment epithelial cells. J Biol Chem 277:3318-24
Chen, P; Lee, T D; Fong, H K (2001) Interaction of 11-cis-retinol dehydrogenase with the chromophore of retinal g protein-coupled receptor opsin. J Biol Chem 276:21098-104
Chen, P; Hao, W; Rife, L et al. (2001) A photic visual cycle of rhodopsin regeneration is dependent on Rgr. Nat Genet 28:256-60
Yang, M; Wang, X G; Stout, J T et al. (2000) Expression of a recombinant human RGR opsin in Lentivirus-transduced cultured cells. Mol Vis 6:237-42
Hao, W; Fong, H K (1999) The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium. J Biol Chem 274:6085-90

Showing the most recent 10 out of 19 publications