Subtraction Analysis of Trabecular Meshwork Genes

Dr. Tamm has previously identified three genes, pax-6, uteroglobulin and thrombospondin-1 that are differentially expressed in a murine trabecular meshwork (TM) cell line under differentiating or non-differentiating conditions. The goal of this proposal is to examine the role of these three genes in glaucoma with the use of various knockout mice. It is hypothesized that pax-6 is the major control gene for TM development. Dr. Tamm is working to determine if pax-6 acts directly on the development of the TM or indirectly via its induction of other factors in lens, iris/ciliary epithelium or retina. He also hopes to determine if a deficiency or lack of uteroglobulin expression leads to morphological and functional changes in the anterior eye segment and TM, comparable to that seen in glaucoma associated with pigment dispersion syndrome. He is also examining thrombospondin-1 expression in the regulation of TGF-beta and TGF-beta controlled genes. Thrombospondin-1 is expressed in the TM and is an activator of TGF-beta, which is found at high levels in the aqueous humor of eyes with primary open-angle glaucoma (POAG). He will analyze the TM phenotype in mice lacking the expression of thrombospondin-1. It is hoped that the proposed studies will lead to a better understanding of the etiology of both congenital glaucoma and POAG by better understanding the molecular biology of the TM, the specialized tissue through which the aqueous fluid drains. This project is a continuation of a study by the same name, begun in 2000.