Abstract
Abstract: :
Purpose: The human trabecular meshwork (HTM) is the main site for aqueous humor drainage and the major regulator of the intraocular pressure. In primary open angle glaucoma (POAG), specific morphological and pathological changes occur in the HTM including increased deposition of extracellular matrix components and a decrease in the number of TM cells. Previous studies have shown biologically active TGFb2 is increased in the aqueous humor (AH) of glaucomatous patients. In addition, we have demonstrated detectable levels of BDNF in human AH. However, the exact role of TGFb2 in POAG is unknown. The purpose of this study was to compare the effects of TGFb2 and BDNF on glaucomatous and normal HTM cells. Methods: Well-characterized normal and glaucomatous HTM cells were treated with either BDNF, TGFb2, or BDNF/TGFb2 in serum free Ham’s nutrient mixture F-10 media for 48 hours. Real time PCR and ELISA assays were used to examine the regulatory effects of BDNF and TGFb2 on each other in HTM cells (mRNA expressions, and secretion). Proliferation studies were done to detect the effects of BDNF and TGFb2 on HTM cell growth rates. Results: There was a reciprocal up-regulation of both mRNA and protein by exposure to either TGFb2 or BDNF in normal HTM cells but variable results were seen with glaucomatous HTM cells. In addition, the combination of TGFb2 and BDNF stimulated cell proliferation in glaucomatous HTM cells but not normal HTM cells. Conclusions: This study demonstrates, for the first time, the differential response to TGFb2 and BDNF by normal and glaucomatous HTM cells. In addition, this study demonstrates the reciprocal up-regulation of TGFb2 and BDNF in cultured normal HTM cells. This raises the possibility that paracrine/autocrine signaling via endogenous growth factors may occur within the HTM.
Keywords: trabecular meshwork • growth factors/growth factor receptors • gene/expression