Identification of TM Cell Markers

Project Summary

Glaucoma is the second leading cause of blindness in the world. Nearly 2.5 million individuals in the US and 70 million worldwide are affected by this blinding disease. Elevated IOP due to reduction in aqueous outflow facility is a major causal risk factor. In humans, the aqueous outflow pathway is constituted of Schlemm's canal (SC) lined by its endothelial cells, and trabecular meshwork (TM) which is divided into the corneoscleral (CS) portion with its endothelial-like TM cells and the juxtacanalicular (JCT) portion with its fibroblast-like TM cells. The functional differences and relative importance of the different cell populations residing in the outflow pathway is a subject of great debate in the field. While the three cell types of the outflow pathway can be readily distinguished in tissue sections based on distinct morphology, no specific markers have been identified that distinguish JCT and CS cells from one another. Clearly, for the analyses and interrogation of each cell type of the aqueous outflow pathway with respect to its role in the outflow resistance and the pathogenesis of glaucoma, availability of robust markers that would permit preparation of pure cultures of each cell type is a prerequisite. In this application we propose studies to identify differential markers of the three distinct cell types of the aqueous outflow pathway using the most modern, state of the art techniques. It is our hope that characterization of gene expression patterns of distinct cell types of the outflow pathway will lay the foundation for research by novel, more accurate approaches for understanding the pathogenic mechanisms of glaucoma.