Melanopsin-Containing ipRGCs Are Resistant to Excitotoxic Injury and Maintain Functional Non-Image Forming Behaviors After Insult in a Diurnal Rodent Model

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for the light signaling properties of non-image forming vision. Melanopsin-expressing ipRGCs project to retinorecipient brain regions involved in modulating circadian rhythms. Melanopsin has been shown to play an important role in how animals respond to light, including photoentrainment, masking (i.e., acute behavioral responses to light), and the pupillary light reflex (PLR). Importantly, ipRGCs are resistant to various forms of damage, including ocular hypertension, optic nerve crush, and excitotoxicity via N-methyl-D-aspartic acid (NMDA) administration. Although these cells are resistant to various forms of injury, the question still remains whether or not these cells remain functional following injury. Here we tested the hypothesis that ipRGCs would be resistant to excitotoxic damage in a diurnal rodent model, the Nile grass rat (Arvicanthis niloticus). In addition, we hypothesized that following insult, grass rats would maintain normal circadian entrainment and masking to light. In order to test these hypotheses, we injected NMDA intraocularly and examined its effect on the survivability of ipRGCs and RGCs, along with testing behavioral and functional consequences. Similar to findings in nocturnal rodents, ipRGCs were spared from significant damage but RGCs were not. Importantly, whereas image-forming vision was significantly impaired, non-image forming vision (i.e, photoentrainment, masking, and PLR) remained functional. The present study aims to characterize the resistance of ipRGCs to excitotoxicity in a diurnal rodent model.