Although multiple small-molecule compounds that bind to and modulate σ2R/TMEM97 function demonstrate beneficial effects on neuroprotection in dry AMD models and age-related neurodegenerative diseases, gain-of-function or loss-of-function studies using cell or animal models with genetic intervention of σ2R/TMEM97 show contradictory results on how σ2R/TMEM97 regulates oxidative stress and cell survival of the RPE. This evidence concerns the gene TMEM97 and dry age related macular degeneration.