Abstract

The 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.

Details

Title
σ2R/TMEM97 in retinal ganglion cell degeneration
Author
Wang, Hua 1 ; Peng, Zhiyou 1 ; Li, Yiwen 1 ; Sahn, James J. 2 ; Hodges, Timothy R. 2 ; Chou, Tsung-Han 1 ; Liu, Qiong 1 ; Zhou, Xuezhi 1 ; Jiao, Shuliang 3 ; Porciatti, Vittorio 1 ; Liebl, Daniel J. 4 ; Martin, Stephen F. 2 ; Wen, Rong 1 

 Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, USA (GRID:grid.26790.3a) (ISNI:0000 0004 1936 8606) 
 University of Texas at Austin, Department of Chemistry and Biochemistry, Austin, USA (GRID:grid.89336.37) (ISNI:0000 0004 1936 9924) 
 Florida International University, Department of Biomedical Engineering, Miami, USA (GRID:grid.65456.34) (ISNI:0000 0001 2110 1845) 
 University of Miami, Miller School of Medicine, Department of Neurosurgery, Miami, USA (GRID:grid.26790.3a) (ISNI:0000 0004 1936 8606) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2743834776
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.