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M John, DA Carper, S Subramanian, RR Wang, W Ma, A Spector; Differential Gene Expression of Matrix Metalloproteinases (MMPs) in an Oxidative Stress Model of Cataract . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2357.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To compare the expression of mRNAs for matrix metalloproteinases (MMPs), membrane type MMPs (MT-MMPs), and tissue inhibitors of MMPs (TIMPs) in rat lenses exposed to oxidative stress in order to define the molecular role of these genes in lens opacification. Methods: Lenses from 4-6 week old rats were subjected to 4 or 7 hours of photochemical stress using 4 µM riboflavin, 4% O2, and light. RNA samples from normal and insulted lenses were used for RT-PCR. Results: RT-PCR analysis showed an approximate 10-fold down regulation of mRNAs for MMP-2 and an approximate 5-fold up regulation of mRNAs for MMP-9 at 4 and 7 hours of oxidative stress. MT1-MMP and MT3-MMP were down regulated over 5-fold at 4 hours and over 9-fold at 7 hours. TIMP-1, -2 and -3 were unchanged at 4 hours. TIMP-1 and -3 were down regulated approximately 2-fold at 7 hours, while TIMP-2 was unchanged. No significant difference between control and treated lens mRNAs was observed for glutathione peroxidase, mitochondrial cytochrome b, GAPDH, catalase, or tubulin. However, beta-actin mRNA was up regulated 5-fold and 9-fold in treated lenses at 4 and 7 hours, respectively. Conclusions: Photochemical stress induced differential gene expression of matrix metalloproteinases, while metalloproteinase inhibitors were only slightly affected. The inverse relationship between MMP-2 and MMP-9 is consistent with the view that the MMP-9 promoter is inducible by a number of stresses, while the MMP-2 promoter tends to be constitutive. In the present study, MMP-9 mRNAs increase and MMP-2 mRNAs decrease, suggesting independent functional requirements during oxidative stress.
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