LTBP2 knockdown and oxidative stress affect glaucoma features including TGFβ pathways, ECM genes expression and apoptosis in trabecular meshwork cells.

Glaucoma is the leading cause of irreversible blindness worldwide. Although the etiology of glaucoma is incompletely understood, it is known that the extracellular matrix (ECM) of the trabecular meshwork, oxidative stress, TGFβ signaling pathways, and apoptosis are important components of glaucoma pathogenesis. These components appear to be interrelated, but knowledge on their interactions remains incomplete. Relevant to this gap in knowledge, LTBP2, glaucoma causing gene, may also be related to the mentioned components of glaucoma pathogenesis because of its putative roles in TGFβ signaling and ECM functions. This background prompted us to further query interactions among some molecules and pathways thought to be important in glaucoma etiology, with emphasis on oxidative stress and LTBP2. To this end, effects of LTBP2 siRNA knockdown, oxidative stress induction, TGFβ2 and gremlin exposures on canonical TGFβ and BMP signaling pathways, expression of ECM related genes, and apoptosis were assayed in primary human trabecular meshwork cell cultures. We found that oxidative stress induction and LTBP2 knockdown both affected all the processes queried, and that their affects paralleled one another. We suggest that effects of both oxidative stress and LTBP2 knockdown on the ECM and apoptosis may be mediated by TGFβ and BMP signaling pathway activation.