The overall objective of the research program is to elucidate molecular mechanisms which are important in biological systems. The system being studied is the vertebrate photoreceptor. A major emphasis of the research plan is to combine electrophysiological, metabolic, biochemical and rhodopsin studies to provide some understanding of the functioning of the vertebrate photoreceptor. The uniqueness of the approach is the variety of techniques which are applied to studies of the system and the use, when possible, of excised retinas which are physioloically active. One study is on the role of cGMP in the vertebrate photoreceptor. As a major part of this study a chemical change of the perfusate is used to alter the cGMP concentration of the photoreceptor wihtin normal physiological limits and its electrophysiological and metabolic consequences are investigated. Another study is the role of energy consuming processes in the functioning of the photoreceptor. In one aspect of this study various ions and inhibitors are used to alter the ATP concentration of the photoreceptor and the functional and oxygen consumption properties of the cell. Another area of study are the reactions and conformation changes of rhodopsin. The conformation changes of rhodopsin during its photolysis, the molecular mechanisms involved in these conformation changes and the role of rhodopsin in the functioning and maintenance of the photoreceptor are some of the questions being approached. Phototransduction mutants of Drosophila are also used to study the functioning of the photoreceptors. Using single gene lesions of Drosophila, which have their primary effect on a single polypeptide, it is possible to observe interactions between the phototransduction process and the processes responsible for the maintenance of the rhodopsin concentration and sturctural integrity of the cell. In addition to providing information on cellular interactions, this genetic approach may be usable to identify unknown components in the phototransduction process.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000413-18
Application #
3255324
Study Section
(VID)
Project Start
1977-05-01
Project End
1988-02-29
Budget Start
1985-12-01
Budget End
1988-02-29
Support Year
18
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Purdue University
Department
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Ostroy, S E; Frede, S M; Wagner, E F et al. (1994) Decreased rhodopsin regeneration in diabetic mouse eyes. Invest Ophthalmol Vis Sci 35:3905-9
Ostroy, S E; Gaitatzes, C G; Friedmann, A L (1993) Hypoxia inhibits rhodopsin regeneration in the excised mouse eye. Invest Ophthalmol Vis Sci 34:447-52
Ostroy, S E; Friedmann, A L; Gaitatzes, C G (1992) Extracellular glucose dependence of rhodopsin regeneration in the excised mouse eye. Exp Eye Res 55:419-23
Ostroy, S E; Svoboda, R A; Wilson, M J (1990) A stage in glycolysis controls the metabolic adjustments of vertebrate rod photoreceptors upon illumination. Biochem Biophys Res Commun 168:155-60
Meyertholen, E P; Stein, P J; Williams, M A et al. (1987) Studies of the Drosophila norpA phototransduction mutant. II. Photoreceptor degeneration and rhodopsin maintenance. J Comp Physiol A 161:793-8
Cocozza, J D; Ostroy, S E (1987) Factors affecting the regeneration of rhodopsin in the isolated amphibian retina. Vision Res 27:1085-91
Wilson, M J; Ostroy, S E (1987) Studies of the Drosophila norpA phototransduction mutant. I. Electrophysiological changes and the offsetting effect of light. J Comp Physiol A 161:785-91
Meyertholen, E P; Wilson, M J; Ostroy, S E (1986) The effects of hepes, bicarbonate and calcium on the cGMP content of vertebrate rod photoreceptors and the isolated electrophysiological effects of cGMP and calcium. Vision Res 26:521-33