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Light, Melanopsin, and Retinal Development: A Comprehensive Characterization of Intrinsically Photosensitive Retinal Ganglion Cells in the Postnatal Retina

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Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) represent a class of non-canonical, ganglion cell photoreceptors. These cells influence a variety of visual behaviors including contrast sensitivity, circadian photoentrainment, sleep, and even mood. These wide-ranging behavioral influences are attributed to the multiple subtypes (M1-6) that comprise the ipRGC population, with different subtypes possessing a unique complement of cellular properties and playing distinct roles in vision. Although ipRGCs have been categorized based on their adult characteristics, they are in fact light sensitive from embryonic stages and begin to exhibit diverse light response properties at early postnatal stages. Thus, these unique photoreceptors are light sensitive long before the rest of the retinal circuitry is able to functionally relay rod/cone signals (~Postnatal day 12 in mice, at eye opening). This early photosensitivity has led to multiple studies examining potential developmental influences of ipRGCs on the developing retina and visual system. One study found that melanopsin modulates the branching patterns of retinal vasculature in a light-dependent manner. Other studies revealed that melanopsin and ipRGCs can influence spontaneous retinal waves and that they are important for retinofugal refinement. Surprisingly, light and melanopsin can even drive light avoidance behavior in neonatal mice as young as 6 days old. As the first light responsive cell in the retina, ipRGCs are poised to be the only cell type to modulate the developing retina in a light dependent manner. However, the extent of their influence is unknown. Furthermore, it is not clear how ipRGCs themselves develop and how their properties change over the timespan that the retina is developing. Though recent evidence suggests that ipRGCs have early and unexpected influences on retinal and visual system development, the extent and mechanisms of this influence are not well-understood. One major limitation in understanding the role of ipRGCs during development is our incomplete understanding of the physiological, morphological, and light-signaling properties of ipRGC subtypes during retinal development. While there have been a few studies describing some features of ipRGCs during development, we are lacking a systematic study of the properties of individual, identified ipRGC subtypes at discrete time points during development. Furthermore, though studies have begun to address the influence of light signaling through ipRGCs on retinal and visual system development, whether environmental light influences ipRGC development is also unknown. The following work seeks to close some of these information gaps and define various ipRGC properties during postnatal retinal development. We take both a molecular and physiological approach to identify key components of ipRGC development as well as gain some insight to their impact on the developing retina.

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