Phototransduction is a series of enzymatic events within retinal photoreceptor cells that converts light to chemical and electrical energy. Light activates the visual photopigment rhodopsin, leading to activation of phosphodiesterase (PDE) which hydrolyzes cyclic GMP (cGMP) to GMP. The decline in cGMP levels closes cGMP-gated sodium/calcium channels resulting in photoreceptor hyperpolarization. A new enzyme was recently discovered in the bovine retina. This enzyme, recovering, is a 26 kilodalton calcium-binding protein that is thought to reverse the effects of light on cGMP levels by activating guanylate cyclase. Guanylate cyclase produces cGMP to overcome the cGMP- hydrolyzing effect of PDE, and reopens the sodium/calcium channels in photoreceptor outer segments. A recovering-like protein may also be present in some bipolar cells. We have recently cloned and sequenced two closely related forms of recovering in human retina. The goal of the proposed research is to utilize specific nucleotide and immunochemical probes to identify the cellular sites of recovering synthesis in the human retina, and to characterize the regulation of recovering gene expression. We also propose to characterize and further develop polymorphic sequences at the recovering locus. These markers can eventually be used to determine if the recovering gene is genetically-linked to loci responsible for inherited diseases of vision. Many investigators suspect that the various forms of retinitis pigmentosa may be due to abnormalities of proteins involved in phototransduction. The important role of recovering in visual transduction makes it plausible that mutations in the gene encoding recovering could be responsible for a form of retinal degeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
7R01EY010081-03
Application #
2163764
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1993-05-01
Project End
1996-04-30
Budget Start
1994-08-01
Budget End
1995-04-30
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Boston University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Wiechmann, Allan; Howard, Eric (2003) Functional analysis of the human recoverin gene promoter. Curr Eye Res 26:25-32
Wiechmann, A F; Sinacola, M K (1997) Diurnal expression of recoverin in the rat retina. Brain Res Mol Brain Res 45:321-4
Yan, X X; Wiechmann, A F (1997) Early expression of recoverin in a unique population of neurons in the human retina. Anat Embryol (Berl) 195:51-63
Wiechmann, A F; Wirsig-Wiechmann, C R (1994) Melatonin receptor distribution in the brain and retina of a lizard, Anolis carolinensis. Brain Behav Evol 43:26-33
Wiechmann, A F; Haro, K C; Bowden, D W (1994) Three microsatellite polymorphisms at the recoverin locus on chromosome 17. Hum Mol Genet 3:1028
Wiechmann, A F; Akots, G; Hammarback, J A et al. (1994) Genetic and physical mapping of human recoverin: a gene expressed in retinal photoreceptors. Invest Ophthalmol Vis Sci 35:325-31
Wiechmann, A F; Hammarback, J A (1993) Molecular cloning and nucleotide sequence of a cDNA encoding recoverin from human retina. Exp Eye Res 56:463-70
Wiechmann, A F; Hammarback, J A (1993) Expression of recoverin mRNA in the human retina: localization by in situ hybridization. Exp Eye Res 57:763-9