DESCRIPTION (provided by applicant): Loss of sight in glaucomatous optic neuropathy is due to the death of retinal ganglion cells (RGC). Our long-term goal is to test the hypothesis that dysfunction of RGC precedes their death in early stages of glaucomatous optic neuropathy, and that vision may be spared if this dysfunction is first detected and then treated. Our immediate goal is to understand the relationships between potentially reversible functional changes and irreversible structural changes of RGC in the progression of glaucoma. Our collaborative research team combines expertise in glaucoma, visual electrophysiology, biophysics, and retinal imaging, working in a unique clinical-research setting that has a large number of patients with suspicion of glaucoma including high rates of individuals of African American and Hispanic descent. We will use non-invasive techniques that we developed to evaluate RGC function and structure - including the pattern electroretinogram (PERG) to measure potentially reversible functional changes of RGC, and Optical Coherence Tomography (OCT) to measure irreversible structural changes of RGC and their axons - in selected groups of these patients. We will also use non-invasive paradigms - suction cup to increase the intraocular pressure (IOP) and topical treatment to lower IOP - to establish whether PERG abnormalities depend on IOP. The specific aims are: 1) to identify and characterize PERG abnormalities in glaucoma suspects, 2) to understand the relationship between PERG losses and OCT losses, and 3) to understand the relationship between PERG abnormalities and induced changes in IOP. This combined, innovative approach will yield a better understanding of the pathophysiological mechanisms in the progression of glaucomatous neuropathy, may provide a rationale for treatment or prevention of glaucoma, and will develop a method to monitor the efficacy of treatment based on RGC function.