Growth factor and cytokine modulation of trabecular meshwork matrix metalloproteinase and TIMP expression

Current Eye Research
J P AlexanderT S Acott

Abstract

We hypothesize that regulated trabecular extracellular matrix (ECM) turnover, initiated by the matrix metalloproteinases, is critical for the maintenance of normal aqueous humor outflow rates. However, very little is known about the regulation of trabecular ECM turnover. To identify candidate trabecular regulators, we evaluated the effects of several growth factors and cytokines on trabecular matrix metalloproteinase and TIMP expression. Porcine trabecular meshwork cells were treated with several doses of a variety of growth factors and cytokines and culture media was analyzed after 24, 48, and 72 h. Zymograms were used to evaluate stromelysin, gelatinase A and B activity levels, while immunoblots of Western transfers were used to evaluate stromelysin, collagenase, TIMP-1 and TIMP-2 protein levels. A phorbol mitogen (TPA), and TNF alpha and beta, interleukin-1 alpha and PDGF BB stimulate gelatinase B, stromelysin, interstitial collagenase and TIMP-1 expression, while having negligible effects on gelatinase A expression; TIMP-2 levels are reduced by TNF but not affected by the other treatments. Acidic and basic FGF, IL-1 beta, TGF beta and PDGF AB produce similar but smaller effects, while HGF, VEGF, EGF, KGF, and LIF produce sm...Continue Reading

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