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σ2R/TMEM97 in retinal ganglion cell degeneration
Hua Wang1, Zhiyou Peng1, Yiwen Li1
1Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, 33136, USA.
Scientific Reports
|December 1, 2022
Summary
Inhibiting sigma 2 receptor (σ2R)/transmembrane protein 97 (TMEM97) protects retinal ganglion cells from ischemic injury. This finding offers a new therapeutic target for neurodegenerative diseases affecting the eye.
Area of Science:
- Neuroscience
- Cell Biology
- Ophthalmology
Background:
- The sigma 2 receptor (σ2R) is identified as transmembrane protein 97 (TMEM97), an endoplasmic reticulum membrane protein.
- σ2R/TMEM97 ligands exhibit neuroprotective properties, indicating its involvement in neurodegeneration.
Purpose of the Study:
- To investigate the role of σ2R/TMEM97 in retinal ganglion cell (RGC) degeneration following ischemic injury.
- To evaluate the neuroprotective potential of inhibiting σ2R/TMEM97 in RGCs.
Main Methods:
- Characterization of ischemia-induced RGC degeneration in TMEM97 knockout (TMEM97-/-) mice.
- Assessment of RGC survival after intravitreal injection of a selective σ2R/TMEM97 ligand (DKR-1677) in wildtype mice.
Main Results:
- RGCs in TMEM97-/- mice demonstrated resistance to ischemia-induced degeneration.
- DKR-1677 treatment significantly protected RGCs from degeneration in wildtype mice.
- σ2R/TMEM97 facilitates RGC death after ischemic injury.
Conclusions:
- σ2R/TMEM97 plays a critical role in promoting RGC death following ischemic events.
- Inhibition of σ2R/TMEM97 function is a viable neuroprotective strategy for RGCs.
- Targeting σ2R/TMEM97 offers a promising therapeutic avenue for RGC degenerative diseases.
