Our goal is to understand the process of visual transduction. Only when this mechanism is fully elucidated can one design meaningful approaches to visual disorders arising from the malfunction of this transduction process. Our hypothesis is that by using retinal analogues to specifically induce changes deep within the rhodopsin protein, it may be possible to modify the transduction mechanism. Our approach is to use analogues of the native chromophore, 11-cis retinal, to probe the site at which the visual process is initiated. The retinal analogues present the unique opportunity to gain information on changes within the rhodopsin protein itself without disrupting the native system. By using a variety of analogues to test specific chemical and electronic interactions of the chromophore with the protein, we propose to undertake the following series of experiments in collaboration with other laboratories: 1) Incorporation of analogues into the living isolated photoreceptors of vertebrate (tiger salamander) and an invertebrate (Limulus) for the purpose of studying effects on the discrete electrical events in transduction. 2) Correlation of G protein and phosphodiesterase activation with metarhodopsin states of the analogue pigments. 3) Determination of the exact location of the chromophore within the visual pigment in the rhodopsin and metatrhodopsin states by photoaffinity labeling followed by mass spectral analysis. 4) Studies of the structure-function role of retinal in a number of aspects of rhodopsin chemistry. 5) Determination in vitro of the properties of invertebrate analogue pigments. These studies will generate a better understanding of the transduction process which may have important implications in certain human disease processes.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004939-08
Application #
3259603
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-08-01
Project End
1993-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Bowrey, Hannah E; Anderson, David M; Pallitto, Patrick et al. (2016) Imaging mass spectrometry of the visual system: Advancing the molecular understanding of retina degenerations. Proteomics Clin Appl 10:391-402
Tang, Peter H; Crouch, Rosalie K (2015) Sustained delivery of retinoids to prevent photoreceptor death. Methods Mol Biol 1271:363-8
Crouch, Rosalie K; Koutalos, Yiannis; Kono, Masahiro et al. (2015) A2E and Lipofuscin. Prog Mol Biol Transl Sci 134:449-63
Ablonczy, Zsolt; Smith, Noah; Anderson, David M et al. (2014) The utilization of fluorescence to identify the components of lipofuscin by imaging mass spectrometry. Proteomics 14:936-44
Ablonczy, Zsolt; Higbee, Daniel; Grey, Angus C et al. (2013) Similar molecules spatially correlate with lipofuscin and N-retinylidene-N-retinylethanolamine in the mouse but not in the human retinal pigment epithelium. Arch Biochem Biophys 539:196-202
Ablonczy, Zsolt; Higbee, Daniel; Anderson, David M et al. (2013) Lack of correlation between the spatial distribution of A2E and lipofuscin fluorescence in the human retinal pigment epithelium. Invest Ophthalmol Vis Sci 54:5535-42
Tang, Peter H; Kono, Masahiro; Koutalos, Yiannis et al. (2013) New insights into retinoid metabolism and cycling within the retina. Prog Retin Eye Res 32:48-63
Bandyopadhyay, Mausumi; Kono, Masahiro; Rohrer, Bärbel (2013) Explant cultures of Rpe65-/- mouse retina: a model to investigate cone opsin trafficking. Mol Vis 19:1149-57
Frederiksen, Rikard; Boyer, Nicholas P; Nickle, Benjamin et al. (2012) Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods. J Gen Physiol 139:493-505
Boyer, Nicholas P; Tang, Peter H; Higbee, Daniel et al. (2012) Lipofuscin and A2E accumulate with age in the retinal pigment epithelium of Nrl-/- mice. Photochem Photobiol 88:1373-7

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