Previous ultrastuctural and histochemical investigations by others have provided qualitative evidence suggesting that the outflow obstruction in primary open-angle glaucoma (POAG) is due to abnormal accumulation of extracellular matrix materials in the trabecular meshwork. New micromethods developed in our laboratories now allow us to 1) biochemically measure and characterize the glycosaminoglycans (GAGs) of a single human trabecular meshwork, and 2) to perform quantitative histochemical analysis of the GAGs in specific regions of the meshwork. With these new tools, we propose to study the GAG composition and localization in human trabecular meshworks from eyebank eyes of POAG donors and age-matched controls, obtained from a national registry and our own donor program. The histochemical method will also be performed upon surgical specimens obtained from POAG eyes and eyes with secondary open-angle glaucomas (treatment controls). In companion studies, the trabecular meshwork from the opposite eyes of POAG and normal donors will be placed in organ and/or cell culture, and the profile of radiolabeled GAG systhesis and turnover determined. The goal of the culture work will be to determine whether any abnormalities in GAG content or composition demonstrated in vivo are expressed in vitro, so that they might be traced to underlying biochemical mechanisms.
