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In the retina, melatonin increases photoreceptor sensitivity to light at night, but not in mice deficient in the melatonin receptor MT1. Baba et al. found that two melatonin receptors, the G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) MT1 and MT2, were both present in the photoreceptor cells of mice, and, when coexpressed in cultured cells, these receptors formed homomeric and heteromeric complexes. Mice deficient in MT2 or expressing a mutant form of MT2 failed to respond to melatonin, suggesting that MT1 and MT2 may function as a heteromeric complex to mediate this response. By testing the response in the presence of various pharmacological agents, melatonin mediated its effect on photoreceptor responses in vivo through the inositol trisphosphate to protein kinase C pathway. Thus, this study delineates a pathway by which melatonin affects vision and provides in vivo evidence for functional GPCR heteromers.
How do Circadian Rhythms Influence Vision?
Circadian rhythms are fluctuations in biological process that occur on a daily basis. These rhythms provide a selective advantage to organisms by allowing them to anticipate regular changes in their environment that occur as the day progresses. The daily, solar cycle of light and darkness is generally considered to be the most powerful entrainment stimulus. The retina is a remarkably rhythmic tissue, with many cellular, biochemical, and physiological processes expressed in a circadian fashion. It is generally accepted that these retinal circadian rhythms allow the organism to anticipate and cope with the more than 1 million-fold change in light intensity from night to day and to optimize visual function for each intensity. The functioning and the role of the retinal circadian clock in mediating retinal physiology is the focus of the research in my laboratory.
Kenkichi Baba, Ph.D.
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