Extracellular Vesicles and Glaucoma: Opportunities and Challenges.

Purpose: Glaucoma is one of the leading causes of irreversible blindness, characterized by progressive visual field loss. Several risk factors are associated with developing the disease. However, the exact mechanisms or pathological pathways involved are still unknown. There is an urgent need to find the mechanisms and biomarkers for early detection and therapy to halt progression or cure the disease. Extracellular vesicles (EVs), specifically exosomes, have emerged as a crucial player in all aspects of glaucoma, including pathogenesis to therapeutic application with their cell-cell communication properties.

Methods: We performed a literature search on PubMed, Google Scholar, and Web of Science using different keywords. Next, we reviewed the literature with studies focusing on the role of EVs as a causative factor in disease progression, biomarker discovery based on their contents, and protection from glaucoma.

Results: Studies summarized here provide reports of differential EV miRNA and protein expression alterations when communicating with aqueous humor drainage tissues. We described how EV contents are involved in various pathways, including extracellular matrix remodeling and miRNA-mediated oxidative stress transmission between outflow tissues, thereby contributing to glaucoma. Extracellular vesicles, mainly derived from mesenchymal stem cells protecting the optic nerve from degeneration, have also been discussed as potential therapies for glaucoma.

Conclusions: Overall, this review provides a comprehensive discussion of the role of extracellular vesicles in glaucoma. We identified the challenges in finding major signaling molecules of glaucoma etiology. Lastly, we highlighted future directions to improve the treatment of glaucoma by extracellular vesicles.