Fei Fei, Li Juan, Rao Wei, Liu Wenbo, Chen Xiaoyan, Su Ning, Wang Yusheng, Fei Zhou
Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, 71032, People's Republic of China.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, People's Republic of China.
Cell Mol Neurobiol. 2015 Oct;35(7):1039-48. doi: 10.1007/s10571-015-0198-2. Epub 2015 Apr 30.
Retinal ischemia and reperfusion (I/R) is extensively involved in ocular diseases, causing retinal ganglion cell (RGCs) death resulting in visual impairment and blindness. Homer1a is considered as an endogenous neuroprotective protein in traumatic brain injury. However, the roles of Homer1a in RGCs I/R injury have not been elucidated. The present study investigated the changes in expression and effect of Homer1a in RGCs both in vitro and in vivo after I/R injury using Western blot, TUNEL assay, gene interference and overexpression, and gene knockout procedures. The levels of Homer1a and phosphorylated Erk (p-Erk) increased in RGCs and retinas after I/R injury. Upregulation of Homer1a in RGCs after I/R injury decreased the level of p-Erk, and mitigated RGCs apoptosis. Conversely, downregulation of Homer1a increased the level of p-Erk, and augmented RGCs apoptosis. Furthermore, inhibition of the p-ERK reduced RGCs apoptosis, and increased the expression of Homer 1a after I/R injury. Finally, the retinas of Homer1a KO mice treated with I/R injury had significantly less dendrites and RGCs, compared with Homer1a WT mice. These findings demonstrated that Homer1a may contribute to RGCs survival after I/R injury by interacting with Erk pathway.
视网膜缺血再灌注（I/R）广泛参与眼部疾病，导致视网膜神经节细胞（RGCs）死亡，进而造成视力损害和失明。Homer1a被认为是创伤性脑损伤中的一种内源性神经保护蛋白。然而，Homer1a在RGCs缺血再灌注损伤中的作用尚未阐明。本研究采用蛋白质免疫印迹法、TUNEL检测法、基因干扰与过表达以及基因敲除方法，研究了缺血再灌注损伤后体外和体内RGCs中Homer1a的表达变化及其作用。缺血再灌注损伤后，RGCs和视网膜中Homer1a及磷酸化细胞外信号调节激酶（p-Erk）水平升高。缺血再灌注损伤后RGCs中Homer1a的上调降低了p-Erk水平，并减轻了RGCs凋亡。相反，Homer1a的下调增加了p-Erk水平，并加剧了RGCs凋亡。此外，抑制p-ERK可减少缺血再灌注损伤后RGCs凋亡，并增加Homer 1a的表达。最后，与野生型Homer1a小鼠相比，缺血再灌注损伤处理的Homer1a基因敲除小鼠的视网膜中树突和RGCs明显减少。这些研究结果表明，Homer1a可能通过与Erk通路相互作用，有助于缺血再灌注损伤后RGCs的存活。
