The overall goal of this project is to gain an understanding of retinal function. For the next 5 years, we are focusing our efforts on attempting to identify the neurotransmitters used by the retinal neurons and especially on the effects these substances have on retinal cells. Much of the work planned will utilize isolated retinal cells maintained in culture for periods of days to weeks. Five specific projects are proposed: 1) Patch and voltage clamping of isolated horizontal and bipolar cells of the carp and skate retina. This project is studying by patch clamping techniques the response of the horizontal cell membrane to L-glutamate and its analogues. We plan in particular to use patch clamp electrodes to voltage clamp the isolated cells in order to study the ion flows that occur in these cells in response to neurotransmitter substances. 2) An analysis of the ionic mechanisms underlying the responses of isolated and cultured horizontal and bipolar cells of the carp and skate retinas to various neurotransmitter agents, and a quantitative evaluation of the effects of neurotransmitter agonists and antagonists on these neurons. For these experiments, drugs or altered Ringer's solution will be applied to the isolated cells by a microperfusion technique. 3) A physiological and pharmacological study of neurons in culture other than horizontal and bipolar cells, and a study of isolated neurons maintained in culture that are derived from animals other than fish. We are particularly interested in maintaining amacrine cells in culture and studying their physiological and pharmacological properties and also studying isolated retinal neurons from a mammal, perhaps rabbit, in culture. 4) A study of synapse formation between neurons maintained in culture and a physiological and pharmacological analysis of such synapses. Initially we plan to study electrical synapse formation between cultured horizontal cells, but eventually we hope to induce and study chemical synapse formation between a variety of retinal cells. 5) An analysis of the effects of drugs and altered Ringer's solution on neurons in the intact perfused retina. These experiments are intended to complement the isolated cell studies by comparing the effects of drugs and/or altered Ringer's solution on isolated cells with the effects of the same treatments on cells in the intact retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000824-17
Application #
3255556
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1979-06-01
Project End
1989-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
17
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Wasfy, Meagan M; Matsui, Jonathan I; Miller, Jessica et al. (2014) myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses. Exp Eye Res 122:65-76
Fadool, James M; Dowling, John E (2008) Zebrafish: a model system for the study of eye genetics. Prog Retin Eye Res 27:89-110
Wong, Kwoon Y; Dowling, John E (2005) Retinal bipolar cell input mechanisms in giant danio. III. ON-OFF bipolar cells and their color-opponent mechanisms. J Neurophysiol 94:265-72
Wong, Kwoon Y; Cohen, Ethan D; Dowling, John E (2005) Retinal bipolar cell input mechanisms in giant danio. II. Patch-clamp analysis of on bipolar cells. J Neurophysiol 93:94-107
Kainz, Pamela M; Adolph, Alan R; Wong, Kwoon Y et al. (2003) Lazy eyes zebrafish mutation affects Muller glial cells, compromising photoreceptor function and causing partial blindness. J Comp Neurol 463:265-80
Mangrum, Wells I; Dowling, John E; Cohen, Ethan D (2002) A morphological classification of ganglion cells in the zebrafish retina. Vis Neurosci 19:767-79
Allwardt, B A; Lall, A B; Brockerhoff, S E et al. (2001) Synapse formation is arrested in retinal photoreceptors of the zebrafish nrc mutant. J Neurosci 21:2330-42
Li, L; Dowling, J E (2000) Disruption of the olfactoretinal centrifugal pathway may relate to the visual system defect in night blindness b mutant zebrafish. J Neurosci 20:1883-92
Li, L; Dowling, J E (2000) Effects of dopamine depletion on visual sensitivity of zebrafish. J Neurosci 20:1893-903
Link, B A; Fadool, J M; Malicki, J et al. (2000) The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells. Development 127:2177-88

Showing the most recent 10 out of 52 publications