The presence of melatonin rhythmicity in the retina of mammals has been demonstrated by several in vivo and in vitro studies, but many aspects of its synthesis and regulation in this tissue are still obscure. The goals of the present research proposal are to identify the cell type(s) that synthesizes melatonin and to elucidate the role of environmental light and of the circadian clock in regulating melatonin synthesis in the retina of mammals. The first specific aim will test the hypothesis that cone photoreceptors contain the melatonin synthesizing machinery as well as the circadian clock components to regulate it.
The second aim will test the hypothesis that rod photoreceptors and/or inner retinal neurons contain the circadian clock(s) that drives retinal melatonin biosynthesis in cones. Finally, the third aim will test the hypothesis that cone photopigments mediate the suppression of retinal melatonin that follows exposure nocturnal exposure to light. In our research we will use a wide array of new and technologically advanced techniques such as dual in situ hybridization, quantitative real time PCR and Laser Capture Dissecting Microscopy. Retinal melatonin is involved in the modulation of several aspects of retinal physiology; thus the understanding of how this hormone (neuromodulator) is regulated will likely improve our understanding of retinal physiology and pathologies. Modem life style has tremendously changed our daily exposure to light and darkness and thus it is important to understand the effect that such exposure may have on the organism and, in particular, retinal function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS043459-04
Application #
7008088
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Mitler, Merrill
Project Start
2003-01-15
Project End
2007-07-14
Budget Start
2006-01-01
Budget End
2007-07-14
Support Year
4
Fiscal Year
2006
Total Cost
$277,326
Indirect Cost
Name
Morehouse School of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
102005451
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Tosini, Gianluca; Owino, Sharon; Guillaume, Jean-Luc et al. (2014) Understanding melatonin receptor pharmacology: latest insights from mouse models, and their relevance to human disease. Bioessays 36:778-87
Baba, Kenkichi; Benleulmi-Chaachoua, Abla; Journé, Anne-Sophie et al. (2013) Heteromeric MT1/MT2 melatonin receptors modulate photoreceptor function. Sci Signal 6:ra89
Tosini, Gianluca; Baba, Kenkichi; Hwang, Christopher K et al. (2012) Melatonin: an underappreciated player in retinal physiology and pathophysiology. Exp Eye Res 103:82-9
Baba, Kenkichi; Mazzoni, Francesca; Owino, Sharon et al. (2012) Age-related changes in the daily rhythm of photoreceptor functioning and circuitry in a melatonin-proficient mouse strain. PLoS One 7:e37799
Peachey, Neal S; Ray, Thomas A; Florijn, Ralph et al. (2012) GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet 90:331-9
Tosini, Gianluca; Ye, Keqiang; Iuvone, P Michael (2012) N-acetylserotonin: neuroprotection, neurogenesis, and the sleepy brain. Neuroscientist 18:645-53
Alcantara-Contreras, Susana; Baba, Kenkichi; Tosini, Gianluca (2011) Removal of melatonin receptor type 1 increases intraocular pressure and retinal ganglion cells death in the mouse. Neurosci Lett 494:61-4
Sompol, Pradoldej; Liu, Xia; Baba, Kenkichi et al. (2011) N-acetylserotonin promotes hippocampal neuroprogenitor cell proliferation in sleep-deprived mice. Proc Natl Acad Sci U S A 108:8844-9
Sengupta, Anamika; Baba, Kenkichi; Mazzoni, Francesca et al. (2011) Localization of melatonin receptor 1 in mouse retina and its role in the circadian regulation of the electroretinogram and dopamine levels. PLoS One 6:e24483
Contreras-Alcantara, Susana; Baba, Kenkichi; Tosini, Gianluca (2010) Removal of melatonin receptor type 1 induces insulin resistance in the mouse. Obesity (Silver Spring) 18:1861-3

Showing the most recent 10 out of 36 publications