The quantal response to a single photon is the elemental event in vision. In rods, this discrete electrical event results from activation of an enzyme cascade that closes hundreds of channels in the plasma membrane. Absorption of a photon normally initiates the process of photoexcitation by isomerization of the chromophore retinal from 11-cis to the all-trans configuration within the visual pigment, rhodopsin. After excitation, all- trans retinal is released from the apoprotein opsin, and ultimately replaced with fresh 11-cis retinal supplied by the pigment epithelium. The size and shape of the quantal response are governed by l) the intramolecular events which result in formation of Metarhodopsin II and the exposure of a catalytic binding site for transducin, a GTP-binding protein, 2) deactivation of Metarhodopsin II by phosphorylation of the carboxy terminus and capping by arrestin, 3) nearby molecules of photoactivated rhodopsin that produce background adaptation, 4) nearby molecules of opsin that produce opsin desensitization and 5) the availability of 11-cis retinal to convert opsin to its inactive rhodopsin configuration. The longterm objective of this investigation is to determine the mechanism(s) of retinoid uptake into photoreceptors and to gain a molecular explanation of the influence of the retinoids in the mechanisms of excitation and adaptation. As outlined in the progress report, work initiated in this laboratory has demonstrated that it is possible to manipulate excitation, adaptation and retinoid uptake with analogues of retinal.
The Specific Aims of this proposal are to exploit these observations with an analysis of the physiological activities of selected analogues of retinal in intact cells. To this end, we propose: l) to determine the minimum structural requirements of retinal for the relief of opsin desensitization and for the control of excitation in rods & cones, 2) to identify the biochemical pathway responsible for opsin desensitization. 3) to determine the mechanism of retinoid uptake in rods and cones. The proposed work is addressed to program priorities of the NEI panel on Retinal and Choroidal Diseases. The work addresses fundamental mechanisms of receptor activation and desensitization with health ramifications relating to the efficacy of drugs and to the anomalies of pigment activation and dark adaptation associated with retinitis pigmentosa.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007543-09
Application #
2378065
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1988-03-01
Project End
1999-02-28
Budget Start
1997-03-01
Budget End
1998-02-28
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Pathology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Corson, D Wesley; Pepperberg, David R (2003) Conditioning light differentially desensitizes rod phototransduction mediated by native and 9-demethyl analog visual pigment. Vis Neurosci 20:29-36
Ma, J; Znoiko, S; Othersen, K L et al. (2001) A visual pigment expressed in both rod and cone photoreceptors. Neuron 32:451-61
Corson, D W; Kefalov, V J; Cornwall, M C et al. (2000) Effect of 11-cis 13-demethylretinal on phototransduction in bleach-adapted rod and cone photoreceptors. J Gen Physiol 116:283-97
Li, Z; Zhuang, J; Corson, D W (1999) Delivery of 9-Cis retinal to photoreceptors from bovine serum albumin. Photochem Photobiol 69:500-4
Martinez, L M; Crouch, R K; Corson, D W (1997) Application of a submicroliter spectrophotometer in visual pigment studies. Mol Vis 3:4
Chen, N; Ma, J X; Corson, D W et al. (1996) Molecular cloning of a rhodopsin gene from salamander rods. Invest Ophthalmol Vis Sci 37:1907-13
Corson, D W; Crouch, R K (1996) Physiological activity of retinoids in natural and artificial visual pigments. Photochem Photobiol 63:595-600
Corson, D W; Cornwall, M C; Pepperberg, D R (1994) Evidence for the prolonged photoactivated lifetime of an analogue visual pigment containing 11-cis 9-desmethylretinal. Vis Neurosci 11:91-8
Corson, D W; Cornwall, M C; MacNichol, E F et al. (1994) Relief of opsin desensitization and prolonged excitation of rod photoreceptors by 9-desmethylretinal. Proc Natl Acad Sci U S A 91:6958-62
Jin, J; Crouch, R K; Corson, D W et al. (1993) Noncovalent occupancy of the retinal-binding pocket of opsin diminishes bleaching adaptation of retinal cones. Neuron 11:513-22

Showing the most recent 10 out of 13 publications