Melatonin is a methoxyindole synthesized in retinal and pineal gland. In retina, melatonin synthesis occurs primarily in photoreceptors. Retinal melatonin is involved in the regulation of cellular function of photoreceptors retinal pigment epithelial cells, and dopamine neurons. Dopamine regulates melatonin biosynthesis and also directly influences photoreceptor function. A homeostatic relationship between dopamine and melatonin may play a vital role in the circadian or photoperiodic regulation of visual cell functions, such as outer segment membrane turnover. The long-term goal of the study is to characterize the melatonin system of retina and related aspects of visual cell physiology. To this end, cellular and intercellular mechanisms in the regulation of melatonin synthesis and retinal actions will be explored. Specifically, experiments will be conducted (1) to determine the biochemical basis for the coupling of calcium channel activity to cyclic AMP accumulation and melatonin synthesis in photoreceptor cells, (2) to investigate the roles of neurotransmitters in she regulation of melatonin synthesis by light and circadian oscillators, and (3) to investigate the cellular mechanisms for melatonin's actions in the retina, primarily by characterizing the effects of melatonin receptor activation on second messenger systems. These studies involve the use of cell and tissue culture, neuropharmacological, and biochemical methodologies. The research is significant because it will characterize cellular and biochemical systems that play an important role in the regulation of retinal physiology. It is anticipated that characterization of these systems will contribute to the understanding of visual cell physiology and the pathological processes that underlie photoreceptor degeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004864-11
Application #
3259433
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Kang, Seong Su; Ahn, Eun Hee; Zhang, Zhentao et al. (2018) ?-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's disease. EMBO J 37:
Sankaran, Mathangi; Keeley, Patrick W; He, Li et al. (2018) Dopaminergic amacrine cell number, plexus density, and dopamine content in the mouse retina: Strain differences and effects of Bax gene disruption. Exp Eye Res 177:208-212
Kim, Moon K; Aung, Moe H; Mees, Lukas et al. (2018) Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice. Invest Ophthalmol Vis Sci 59:572-581
Chakraborty, Ranjay; Ostrin, Lisa A; Nickla, Debora L et al. (2018) Circadian rhythms, refractive development, and myopia. Ophthalmic Physiol Opt 38:217-245
Mui, Amanda M; Yang, Victoria; Aung, Moe H et al. (2018) Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina. PLoS One 13:e0192435
Vancura, Patrick; Csicsely, Erika; Leiser, Annalisa et al. (2018) Rhythmic Regulation of Photoreceptor and RPE Genes Important for Vision and Genetically Associated With Severe Retinal Diseases. Invest Ophthalmol Vis Sci 59:3789-3799
Zhang, Zhentao; Kang, Seong Su; Liu, Xia et al. (2017) Asparagine endopeptidase cleaves ?-synuclein and mediates pathologic activities in Parkinson's disease. Nat Struct Mol Biol 24:632-642
Kang, Seong Su; Zhang, Zhentao; Liu, Xia et al. (2017) ?-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation. Proc Natl Acad Sci U S A 114:1183-1188
Zhou, Xiangtian; Pardue, Machelle T; Iuvone, P Michael et al. (2017) Dopamine signaling and myopia development: What are the key challenges. Prog Retin Eye Res 61:60-71
Haque, Rashidul; Iuvone, P Michael; He, Li et al. (2017) The MicroRNA-21 signaling pathway is involved in prorenin receptor (PRR) -induced VEGF expression in ARPE-19 cells under a hyperglycemic condition. Mol Vis 23:251-262

Showing the most recent 10 out of 141 publications