Work

Transmembrane Protein 97 (TMEM97): Molecular Target and Treatment in Age-Related Macular Degeneration (AMD)

Year: 2025

Type: review

Abstract: Age-related macular degeneration (AMD) is a common eye disease that significantly affects daily activities and impedes the quality of life in aging adults, yet effective treatments to halt or reverse disease progression are currently lacking. Ongoing research aims at understanding the complex mechanisms underlying AMD pathophysiology involving retinal pigment epithelium (RPE) dysfunction, drusen formation, inflammation, neovascularization, and RPE/photoreceptor degeneration. Sigma 2 receptor/transmembrane protein 97 (σ2R/TMEM97) is a multifunctional protein implicated in cellular processes including cholesterol homeostasis, lysosome-dependent autophagy, calcium homeostasis, and integrated stress response (ISR). Recent genome-wide association studies (GWASs) have identified σ2R/TMEM97 as a novel genetic risk factor strongly associated with AMD development. In this review, we summarize recent research progress on σ2R/TMEM97 in age-related neurodegenerative diseases, highlighting its implication as a molecular target in AMD via regulating oxidative stress, inflammation, lipid uptake, drusen formation, and epithelial–mesenchymal transition (EMT). We also discuss the potential of modulating σ2R/TMEM97 function with novel small-molecule drugs as a promising treatment for dry AMD and the unresolved questions in understanding the mechanistic basis of their actions.

Source: Biomolecules

DOI: 10.3390/biom15091228

Authors: Alyssa Stathopoulos, Joshua J. Wang, Stephen F. Martin, Sarah X. Zhang

Institutions: University at Buffalo, State University of New York, The University of Texas at Austin

Language: English

Topic: Retinal Diseases and Treatments

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258