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Upregulation of Homer1a Promoted Retinal Ganglion Cell Survival After Retinal Ischemia and Reperfusion via Interacting with Erk Pathway

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Abstract

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.

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Abbreviations

I/R:

Ischemia and reperfusion

RGC:

Retinal ganglion cell

p-Erk:

Phosphorylated Erk

IOP:

Intraocular pressure

mGluRs:

Metabotropic glutamate receptors

CC:

Coiled-coil

WT:

Wild type

KO:

Knockout

PBS:

Phosphate-buffered saline

shRNA:

Short hairpin RNA

OGD:

Oxygen and Glucose Deprivation

TBI:

Traumatic brain injury

TUNEL:

TdT-mediated dUTP nick end-labeling

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Acknowledgments

We express our thanks to Professors Bo Xiao and Paul Worley for providing the Homer1a KO mice. This study was supported by the National Natural Science Foundation of China (Nos. 81430043 and 30930093), the National Science and Technology Major Project of China (2013ZX 09J13109-02C), the National Science and Technology Pillar Program of China (No. 2012BAI11B02), and the Science and Technology Project of Shaanxi (No. 2013KTCQ03-01).

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    Authors and Affiliations

    1. Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an, 71032, People’s Republic of China

      Fei Fei & Yusheng Wang

    2. Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 15 Changle Xi Road, Xi’an, 710032, People’s Republic of China

      Juan Li, Wei Rao, Wenbo Liu, Xiaoyan Chen, Ning Su & Zhou Fei

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    1. Fei Fei
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    Correspondence to Yusheng Wang or Zhou Fei.

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    Fei Fei, Juan Li and Wei Rao have contributed equally to this work.

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    Fei, F., Li, J., Rao, W. et al. Upregulation of Homer1a Promoted Retinal Ganglion Cell Survival After Retinal Ischemia and Reperfusion via Interacting with Erk Pathway. Cell Mol Neurobiol 35, 1039–1048 (2015). https://doi.org/10.1007/s10571-015-0198-2

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