Abstract 2319 Disambiguation of Glaucoma-Associated Myocilin Mutations: Study of Trafficking, Aggregation, and Degradation

Missense mutations in myocilin are the strongest genetic link to primary open-angle glaucoma. Bona fide glaucoma-causing mutations housed in the myocilin C-terminal olfactomedin (OLF) domain are familial, rare, and cause early-onset vision loss. Disease mutations introduce a toxic gain of function within trabecular meshwork cells of the eye. This toxic gain of function is hallmarked by myocilin misfolding and aggregation in the endoplasmic reticulum (ER). Chronic ER stress eventually leads to trabecular meshwork (TM) cell death, hastening disease progression.