Tissue Transglutaminase in Glaucoma

Tovar-Vidales, Tara, Tissue Transglutaminase in Glaucoma. Doctor of Philosophy (Cell Biology and Genetics), August 2008; 113pp; 0 tables, 23 illustrations, 165 bibliography, 25 titles. Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is the major risk factor for POAG and is due to resistance of aqueous humor (AH) outflow through the trabecular meshwork ™ and Schlemm’s canal. Transforming growth factor-beta2 (TGF-β2) is elevated in the aqueous humor of glaucomatous eyes compared to normal eyes. Thus, TGF-β2 may play a role in regulating IOP. Tissue transglutaminase (TGM2) is a member of the transglutaminase family involved in cross-linking ECM proteins. In POAG, there are increased cross-linked extracellular matrix proteins (ECM) in the TM, and therefore, may result in elevated AH outflow resistance and elevated IOP. In this study, we examined the differences in both protein expression and enzyme activity of TGM2 between normal and glaucomatous TM cells and tissues. The findings demonstrated the presence of TGM2 in normal and glaucomatous cultured TM cells. We also showed that glaucomatous cultured TM cells and tissues have elevated levels of TGM2. Thus, this data suggest that TGM2 may have a pathogenic role in elevated outflow resistance and elevated IOP. Second, we observed the induction of TGM2 by TGF-β1, β2, and β3 in cultured TM cells, suggesting TGF-β isoforms regulate TGM2 protein levels. Finally, we observed that R-Smads and O38 regulated TGM2 protein levels, suggesting TGF-β2 acts through both its canonical and non-canonical signaling pathway to regulate TGM2.