Department of Psychology and Neuroscience Program, Hope College, Holland, MI, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA.
Department of Radiology, Michigan State University, East Lansing, MI, USA.
Neuroscience. 2019 Aug 1;412:105-115. doi: 10.1016/j.neuroscience.2019.05.058. Epub 2019 Jun 7.
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.
内在光敏视网膜神经节细胞 (ipRGC) 对非成像视觉的光信号特性至关重要。表达黑视蛋白的 ipRGC 投射到参与调节昼夜节律的视网膜接受脑区。黑视蛋白在动物对光的反应中起着重要作用，包括光适应、掩蔽（即对光的急性行为反应）和瞳孔光反射 (PLR)。重要的是，ipRGC 对各种形式的损伤具有抗性，包括眼内高压、视神经挤压和通过 N-甲基-D-天冬氨酸 (NMDA) 给药的兴奋性毒性。尽管这些细胞对各种形式的损伤具有抗性，但仍然存在一个问题，即这些细胞在损伤后是否仍然具有功能。在这里，我们测试了以下假设：在昼夜节律啮齿动物模型（尼罗河草鼠（Arvicanthis niloticus））中，ipRGC 对兴奋性毒性损伤具有抗性。此外，我们假设在受到刺激后，草鼠将保持正常的昼夜节律适应和对光的掩蔽。为了检验这些假设，我们向眼内注射 NMDA，检查其对 ipRGC 和 RGC 存活的影响，并测试行为和功能后果。与夜间啮齿动物的发现相似，ipRGC 免受明显损伤，但 RGC 不受损伤。重要的是，虽然成像视觉受到严重损害，但非成像视觉（即光适应、掩蔽和 PLR）仍然具有功能。本研究旨在表征 ipRGC 在昼夜节律啮齿动物模型中对兴奋性毒性的抗性。
