December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Differential Gene Expression of Matrix Metalloproteinases (MMPs) in an Oxidative Stress Model of Cataract
Author Affiliations & Notes
  • M John
    National Eye Institute NIH Bethesda MD
  • DA Carper
    National Eye Institute NIH Bethesda MD
  • S Subramanian
    National Eye Institute NIH Bethesda MD
  • RR Wang
    Department of Ophthalmology Columbia University New York NY
  • W Ma
    Department of Ophthalmology Columbia University New York NY
  • A Spector
    National Eye Institute NIH Bethesda MD
  • Footnotes
    Commercial Relationships   M. John, None; D.A. Carper , None; S. Subramanian , None; R.R. Wang, None; W. Ma , None; A. Spector, None.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 2357. doi:
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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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Abstract

Abstract: : 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.

Keywords: 504 oxidation/oxidative or free radical damage • 338 cataract • 530 proteolysis 
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