Glaucoma is the third leading cause of blindness in the world, affecting over 15 million people in the US. The most common form of glaucoma is adult-onset primary open-angle glaucoma (POAG) (MIM 137760). Despite the open angle, POAG patients typically have obstructed aqueous humor outflow and elevated intraocular pressure. The site of the blockage of the outflow appears to be in the trabecular meshwork, most likely in the extracellular matrix of this filtration apparatus. However, what specifically causes the obstruction of the outflow is not known. One component of the extracellular matrix, the proteoglycans, may be involved in outflow resistance in the filtration aparatus. In this proposal, the investigator seeks to identify trabecular meshwork proteins that may be important in regulating aqueous humor outflow and to clarify the role that these proteins play in trabecular meshwork outflow. The first specific aim will further our work on the location of proteoglycans in the trabecular meshwork with the use of immunohistochemistry. In the second aim the investigator proposes to utilize differental display of mRNA to identify genes expressed uniquely in the trabecular meshwork in normal and glaucomatous eyes. In the third aim they will characterize these differentially expressed proteins to gain insight into how the trabecular meshwork functions. Thus, this study will begin to establish how proteoglycans and differentially expressed trabecular meshwork proteins regulate the outflow through the trabecular meshwork.
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