Upregulation of Homer1a Promoted Retinal Ganglion Cell Survival After Retinal Ischemia and Reperfusion via Interacting with Erk Pathway.
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.
Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, 71032, People's Republic of China.
Fei
F
Fei
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, People's Republic of China.
Juan
J
Li
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, People's Republic of China.
Wei
W
Rao
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, People's Republic of China.
Wenbo
W
Liu
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, People's Republic of China.
Xiaoyan
X
Chen
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, People's Republic of China.
Ning
N
Su
Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, 71032, People's Republic of China. wangys003@126.com.
Yusheng
Y
Wang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi'an, 710032, People's Republic of China. feizhou@fmmu.edu.cn.
Zhou
Z
Fei
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D000072233:Homer Scaffolding Proteins; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins
Erk signaling; Homer1a; Retinal ganglion cells; Retinal ischemia and reperfusion