Author:
Wang Hua,Peng Zhiyou,Li Yiwen,Sahn James J.,Hodges Timothy R.,Chou Tsung-Han,Liu Qiong,Zhou Xuezhi,Jiao Shuliang,Porciatti Vittorio,Liebl Daniel J.,Martin Stephen F.,Wen Rong
Abstract
AbstractThe sigma 2 receptor (σ2R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that σ2R/TMEM97 binding compounds are neuroprotective, suggesting a role of σ2R/TMEM97 in neurodegenerative processes. To understand the function of σ2R/TMEM97 in neurodegeneration pathways, we characterized ischemia-induced retinal ganglion cell (RGC) degeneration in TMEM97−/− mice and found that RGCs in TMEM97−/− mice are resistant to degeneration. In addition, intravitreal injection of a selective σ2R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that σ2R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of σ2R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of σ2R/TMEM97 in RGCs and likely in other σ2R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting σ2R/TMEM97.
Funder
Hope For Vision
Office of Extramural Research, National Institutes of Health
Miami Project to Cure Paralysis
Welch Foundation
Dell Medical School, University of Texas at Austin
Publisher
Springer Science and Business Media LLC
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