Wang Songtao, Gu Dandan, Zhang Peng, Chen Jing, Li Yan, Xiao Honglei, Zhou Guomin
Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Shanghai 200032, PR China.
Neurosci Lett. 2018 Jan 1;662:368-373. doi: 10.1016/j.neulet.2017.10.055. Epub 2017 Nov 2.
Excitotoxicity plays an important role in neuronal loss in glaucoma. Previous studies indicate melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are more injury-resistant. However, whether melanopsin-expressing ipRGCs are resistant to N-methyl-d-aspartate (NMDA) induced excitotoxicity is not well understood. In the present study, we investigated the effects of NMDA-induced excitotoxicity in conventional retinal ganglion cells (RGCs) and melanopsin-expressing ipRGCs in adult mice. The loss of RGCs and the reduction of the thickness of inner plexiform layer (IPL) were studied by histology, immunofluorescence, TUNEL assay and optical coherence tomography (OCT). The remaining conventional RGCs and ipRGCs were quantified on the 1st, 3rd, 7th, and 21st day after NMDA injection using immunofluorescence. NMDA mediated acute and severe damage of conventional RGCs damage in a time-dependent manner, and approximately 85% of the conventional RGCs were lost on the 21st days. Furthermore, a significant reduction of the IPL thickness was observed. Moreover, compared to the PBS-injected eyes, the density of total melanopsin-positive RGCs decreased by 25% on the 1st day after NMDA injection, and then the density was constant at other time points. Our results suggest that melanopsin-expressing ipRGCs are relatively resistant to excitotoxicity induced by NMDA.
兴奋性毒性在青光眼的神经元丢失中起重要作用。先前的研究表明，表达黑视蛋白的内在光敏视网膜神经节细胞（ipRGCs）更具抗损伤能力。然而，表达黑视蛋白的ipRGCs是否对N-甲基-D-天冬氨酸（NMDA）诱导的兴奋性毒性具有抗性尚不清楚。在本研究中，我们研究了NMDA诱导的兴奋性毒性对成年小鼠传统视网膜神经节细胞（RGCs）和表达黑视蛋白的ipRGCs的影响。通过组织学、免疫荧光、TUNEL检测和光学相干断层扫描（OCT）研究了RGCs的丢失和内网状层（IPL）厚度的减少。使用免疫荧光对NMDA注射后第1、3、7和21天剩余的传统RGCs和ipRGCs进行定量。NMDA以时间依赖性方式介导传统RGCs的急性和严重损伤，在第21天时约85%的传统RGCs丢失。此外，观察到IPL厚度显著降低。此外，与注射PBS的眼睛相比，NMDA注射后第1天，总黑视蛋白阳性RGCs的密度降低了25%，然后在其他时间点密度保持恒定。我们的结果表明，表达黑视蛋白的ipRGCs对NMDA诱导的兴奋性毒性具有相对抗性。
