Retinal waves comprise zones of spontaneous activation that propagate across the immature retina. These waves are thought to participate in the development of retinotopic maps and the segregation of binocular inputs to the superior colliculus and lateral geniculate nucleus. Retinal waves occur before rod and cone photoreceptors are mature, at a time when the retina has been considered insensitive to light. However, recent findings invalidate this assumption. There is a novel class of photoreceptor, the intrinsically photosensitive retinal ganglion cell (ipRGC), that is fully functional at this stage. Virtually nothing is known about possible interactions between ipRGCs, light exposure, and retinal waves. This proposal explores not only how these photoreceptors are affected by retinal waves, but also how they, in turn, may affect the waves. In the adult retina, ipRGCs not only receive excitatory and inhibitory synaptic input, but also are thought to feed signals back into the inner retina. This raises the possibility of bidirectional interactions between retinal waves and ipRGCs, although the intraretinal synaptic connectivity of ipRGCs at this developmental stage has not been determined. Preliminary data indicate that not only do ipRGCs discharge in association with retinal waves, but also that photic activation of this class of ganglion cells alters retinal wave activity. Therefore, the specific aims of this proposal are: 1. Characterize excitation of ipRGCs during retinal wave activity and identify the mechanism of activation;2. Test the hypothesis that light-induced activation of ipRGCs alters retinal wave activity and assess the mechanism responsible. These studies will shed new light on the mechanism of retinal wave activity and will extend our understanding of ipRGCs, which play an instructive role in circadian rhythm photoentrainment and the pupillary light reflex.

Public Health Relevance

This study will examine the role of a specialized class of retinal cells in the regulation of normal visual system development. Further, it will shed new light on how these cells function early in development. These cells play a central role in the adult body's response to daylight and therefore, these studies are relevant to such public health issues as jet lag, seasonal affective disorder, circadian disruption in the blind, and the negative consequences of shift work including impaired performance, increased risk of injury and even elevated cancer rates.

National Institute of Health (NIH)
National Eye Institute (NEI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F03B-H (20))
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Agarwal, Neeraj
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Brown University
Schools of Medicine
United States
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Renna, Jordan M; Chellappa, Deepa K; Ross, Christopher L et al. (2015) Melanopsin ganglion cells extend dendrites into the outer retina during early postnatal development. Dev Neurobiol 75:935-46
Renna, Jordan M; Weng, Shijun; Berson, David M (2011) Light acts through melanopsin to alter retinal waves and segregation of retinogeniculate afferents. Nat Neurosci 14:827-9