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Genetic Advances in Ophthalmology: The Role of Melanopsin-Expressing, Intrinsically Photosensitive Retinal Ganglion Cells in the Circadian Organization of the Visual System

Abstract Daily changes in the light-dark cycle are the principal environmental signal that enables organisms to synchronize their internal biology with the 24-hour day–night cycle. In humans, the visual system is integral to photoentrainment and is primarily driven by a specialized class of intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin (OPN4) in the inner retina. These cells project through the retinohypothalamic tract (RHT) to the suprachiasmatic nuclei (SCN) of the hypothalamus, which serves as the body’s master biological clock. At the same time, the retina itself possesses intrinsic circadian oscillations, exemplified by diurnal fluctuations in visual sensitivity, neurotransmitter levels, and outer segment turnover rates. Recently, it has been noted that both central and peripheral oscillators share a molecular clock consisting of an endogenous, circadian-driven, transcription–translation feedback loop that cycles with a periodicity of approximately 24 hours. This review will cover the role that melanopsin and ipRGCs play in the circadian organization of the visual system.