| First Author | Wang H | Year | 2022 |
| Journal | Sci Rep | Volume | 12 |
| Issue | 1 | Pages | 20753 |
| PubMed ID | 36456686 | Mgi Jnum | J:331965 |
| Mgi Id | MGI:7397746 | Doi | 10.1038/s41598-022-24537-3 |
| Citation | Wang H, et al. (2022) sigma(2)R/TMEM97 in retinal ganglion cell degeneration. Sci Rep 12(1):20753 |
| abstractText | The sigma 2 receptor (sigma(2)R) was recently identified as an endoplasmic reticulum (ER) membrane protein known as transmembrane protein 97 (TMEM97). Studies have shown that sigma(2)R/TMEM97 binding compounds are neuroprotective, suggesting a role of sigma(2)R/TMEM97 in neurodegenerative processes. To understand the function of sigma(2)R/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 sigma(2)R/TMEM97 ligand DKR-1677 significantly protects RGCs from ischemia-induced degeneration in wildtype mice. Our results provide conclusive evidence that sigma(2)R/TMEM97 plays a role to facilitate RGC death following ischemic injury and that inhibiting the function of sigma(2)R/TMEM97 is neuroprotective. This work is a breakthrough toward elucidating the biology and function of sigma(2)R/TMEM97 in RGCs and likely in other sigma(2)R/TMEM97 expressing neurons. Moreover, these findings support future studies to develop new neuroprotective approaches for RGC degenerative diseases by inhibiting sigma(2)R/TMEM97. |
