Photoreceptor function depends on maintenance of a delicate balance between the processes of photosensitive membrane assembly and its degradation. These processes occur in a rhythmic fashion in vertebrate retina and understanding the factors controlling rhythmicity may prove important in understanding pathological processes involving photoreceptors. Our goal is to understand the regulation of cyclic photoreceptor metabolism. The processes to be studied are rod photoreceptor disc shedding, cone retinomotor movement and rhythmic melatonin metabolism. Each process exhibits circadian rhythmicity in its activity and in the principal model used in these studies, Xenopus laevis, can be studied in detail in an in vitro preparation, accessible for experimental manipulation. A major goal is to explore the mechanisms by which """"""""melatonin-like"""""""" copmpounds and retinal dopamine interact as signals respectively for darkness and light. Additional studies using in vitro preparations derived from Rana pipiens and from laboratory rats will be used to investigate the mechanisms by which disc shedding is triggered by light and by a circadian clock. We will analyze the properties of a circadian clock localized in the eye by monitoring circadian release of melatonin. These investigations will require the use of in vitro culture, radioimmunoassay, neuropharmacological, biochemical and electrophysiological techniques. It is expected that understanding regulation of rhythmic photoreceptor metabolism will provide a new basis for evaluating mechanisms of pathogenicity in reinal degenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002414-19
Application #
2158424
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1989-07-01
Project End
1996-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
19
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Kansas
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Besharse, Joseph C; McMahon, Douglas G (2016) The Retina and Other Light-sensitive Ocular Clocks. J Biol Rhythms 31:223-43
Carver, Koryn A; Lourim, David; Tryba, Andrew K et al. (2014) Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature. Am J Physiol Cell Physiol 307:C989-98
Fogerty, Joseph; Besharse, Joseph C (2014) Subretinal infiltration of monocyte derived cells and complement misregulation in mice with AMD-like pathology. Adv Exp Med Biol 801:355-63
Toonen, Joseph; Liang, Lina; Sidjanin, Duska J (2012) Waved with open eyelids 2 (woe2) is a novel spontaneous mouse mutation in the protein phosphatase 1, regulatory (inhibitor) subunit 13 like (Ppp1r13l) gene. BMC Genet 13:76
Scoma, Heather Dehlin; Humby, Monica; Yadav, Geetha et al. (2011) The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light. PLoS One 6:e25382
Fogerty, Joseph; Besharse, Joseph C (2011) 174delG mutation in mouse MFRP causes photoreceptor degeneration and RPE atrophy. Invest Ophthalmol Vis Sci 52:7256-66
Insinna, Christine; Luby-Phelps, Katherine; Link, Brian A et al. (2009) Analysis of IFT kinesins in developing zebrafish cone photoreceptor sensory cilia. Methods Cell Biol 93:219-34
Insinna, Christine; Humby, Monica; Sedmak, Tina et al. (2009) Different roles for KIF17 and kinesin II in photoreceptor development and maintenance. Dev Dyn 238:2211-22
Insinna, Christine; Besharse, Joseph C (2008) Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors. Dev Dyn 237:1982-92
Green, Carla B; Douris, Nicholas; Kojima, Shihoko et al. (2007) Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity. Proc Natl Acad Sci U S A 104:9888-93

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