Regulation of connective tissue growth factor expressionin the aqueous humor outflow pathway

[摘要] Purpose: Connective Tissue Growth Factor (CTGF) is aninducible secretory protein known to regulate proliferation andextracellular matrix production in various cell types. We hypothesizethat CTGF plays a critical role in the physiological regulation ofaqueous humor outflow through the trabecular meshwork (TM) byinfluencing extracellular matrix synthesis and organization.Methods: To determine the expression of CTGF in tissues ofthe aqueous outflow pathway, cells obtained from human TM and Schlemm'sCanal (SC) were analyzed by PCR and western blot analysis. To understandthe regulation of CTGF expression in TM cells, TM cells were eithertreated with various physiologic factors or subjected to cyclicalstretch prior to analysis of CTGF expression by RT-PCR and western blotanalysis. To study the effect of increased intraocular pressure on CTGFproduction, we perfused porcine eyes at high pressure (50 mm Hg) for 5h, followed by analysis of CTGF expression by RT-PCR and westernblotting.Results: Treatment of human TM cells treated with eitherserum or transforming growth factor-beta 1 led to a robust stimulation,compared to thrombin, lysophosphatidic acid (LPA), and dexamethasone,which elicited a relatively moderate induction of CTGF expression. Bothhigh pressure perfusion and mechanical stretch were associated withincreases in the levels of CTGF at the protein and transcript levels.Conclusions: This study demonstrates that CTGF expression inTM cells is modulated by several physiological agonists and by increasedocular pressure and mechanical stretch. These results suggest that theregulation of CTGF expression within tissues of the outflow pathway mayplay a role in the homeostasis of intraocular pressure, possibly bymodulation of ECM production in these tissues.

[学科分类] 生物化学/生物物理