Myopia and Glaucoma, Linked via Mechanotransduction Mechanisms Affecting the Ganglion Cell Complex

Project Summary/Abstract Public perception of myopia as a simple inconvenience masks its sight-threatening consequences. Even moderate levels of myopia predispose an individual to glaucoma at rates equal to a hypertensive's risk for cardiovascular disease. Yet, we lack specific diagnostic markers to identify glaucoma in myopic patients. In fact, myopic eyes can exhibit anatomical changes difficult to distinguish from glaucoma. This is alarming because half the world population is predicted to be myopic in 30 years, which will increase significantly the global prevalence of myopic glaucoma and associated visual impairment. Glaucoma is a complex neuropathy that preferentially affects the ganglion cell complex (GCC). Myopia results in significant eye growth, and appears related to glaucoma through its effect on the optic nerve head. However, the mechanisms that link myopia and glaucoma, in particular the effect of myopic growth on the GCC, remain unexplored. We hypothesize that glaucoma and myopia are linked via mechanisms that sense and respond to mechanical stimuli and affect the GCC. The long-term goal of this research is to identify the mechanisms of myopic glaucoma and explore novel neuroprotection therapeutics to prolong ganglion cell function and survival. The overall objectives in this application are to identify early 1) genetic, 2) cellular, 3) structural and 4) functional markers of glaucoma longitudinally as experimental eyes develop progressive myopia compared to eyes induced with glaucoma. The research proposed in this application is innovative because it focuses on identifying key hallmarks of glaucoma comparing unique animal models of myopia and glaucoma that mimic the prolonged exposure to sustained eye growth experienced by human myopic eyes over time, which is fundamental to understanding how glaucoma can originate from myopia. This research will have a direct positive impact as a tool to accelerate the development of novel prevention and diagnostic strategies for myopic glaucoma, and open up new research avenues for pharmacological interventions and experimental therapeutics to prevent glaucomatous impairment in myopic eyes. The proposed research is significant because is expected to provide strong evidence of the unknown nature of the myopia-glaucoma relationship, will help clinicians address the long-standing challenge of diagnosing glaucoma in myopic eyes, epidemiologists refine distribution patterns of myopic glaucoma, public health professionals develop prevention strategies and campaigns, and scientists create new research avenues for myopic glaucoma.