(from the author's abstract): Circadian and efferent modulation of visual sensitivity is the main focus of this project. Circadian clocks in the Limulus brain and Japanese quail eye modulate retinal structure and function in both animals, and clock(s) in the eye and/or brain modulate visual sensitivity in humans. Non circadian efferent input from the brain further modulates the quail retina, and changes in blood glucose further influence human visual sensitivity. Our long range goal is to understand how these modulatory factors adapt vision for essential tasks. This project has three interrelated lines of research with Specific Aims to investigate: 1) circadian modulation of photoreceptor noise by rhodopsin stabilization; 2) circadian modulation of retinal sensitivity by dopamine and melatonin; 3) circadian and metabolic modulation of human vision. The PI proposes to study the circadian modulation of photoreceptor noise by analyzing rhodopsin stabilization in Limulus with a range of techniques including voltage clamp, site-specific mutagenesis, gene expression in Xenopus oocytes and Drosophila eyes. The PI will study the circadian modulation of retinal sensitivity by the putative transmitters dopamine and melatonin in Japanese quail using in situ hybridization , nuclear run-on assays, Rnase protection assays and other cell and molecular biological techniques. We will study the circadian and metabolic modulation of vision in humans of various ages and diabetic conditions using psycho physical methods and FMRI of the visual cortex. The primary tenet of this project is that comprehensive studies of human vision and two suitable animal models will yield new insights on how circadian mechanisms modulate visual sensitivity. These studies may shed light on a possible relationship between photoreceptor noise, circadian rhythms and some forms of degenerative retinal disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000667-28
Application #
6164635
Study Section
Special Emphasis Panel (ZRG1-VISB (03))
Program Officer
Oberdorfer, Michael
Project Start
1977-12-01
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
28
Fiscal Year
2000
Total Cost
$272,726
Indirect Cost
Name
Upstate Medical University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
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Petrs-Silva, Hilda; Dinculescu, Astra; Li, Qiuhong et al. (2011) Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina. Mol Ther 19:293-301
Solessio, Eduardo; Umino, Yumiko; Cameron, David A et al. (2009) Light responses in rods of vitamin A-deprived Xenopus. Invest Ophthalmol Vis Sci 50:4477-86
Ding, Xi-Qin; Harry, Cynthia S; Umino, Yumiko et al. (2009) Impaired cone function and cone degeneration resulting from CNGB3 deficiency: down-regulation of CNGA3 biosynthesis as a potential mechanism. Hum Mol Genet 18:4770-80
Petrs-Silva, Hilda; Dinculescu, Astra; Li, Qiuhong et al. (2009) High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors. Mol Ther 17:463-71
Umino, Yumiko; Solessio, Eduardo; Barlow, Robert B (2008) Speed, spatial, and temporal tuning of rod and cone vision in mouse. J Neurosci 28:189-98
Kim, Ki Hean; Puoris'haag, Mehron; Maguluri, Gopi N et al. (2008) Monitoring mouse retinal degeneration with high-resolution spectral-domain optical coherence tomography. J Vis 8:17.1-11
Everhart, Drew; Stachowiak, Ana; Umino, Yumiko et al. (2008) Loss of visual and retinal function in light-stressed mice. Adv Exp Med Biol 613:157-64
Alexander, John J; Umino, Yumiko; Everhart, Drew et al. (2007) Restoration of cone vision in a mouse model of achromatopsia. Nat Med 13:685-7
Umino, Yumiko; Frio, Bridget; Abbasi, Maryam et al. (2006) A two-alternative, forced choice method for assessing mouse vision. Adv Exp Med Biol 572:169-72

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