Purchase this article with an account.
H.L. Chandler, D.F. Kusewitt, C.M. H. Colitz; Ultraviolet Radiation Induction of MMP Activity in the Cornea . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3756.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To test the hypothesis that ultraviolet radiation (UVR) alters net protease activity in the cornea by modulating matrix–metalloproteinase (MMP–9, MMP–2) activity in corneal epithelial cells and stromal fibroblasts. Methods: Freshly isolated canine corneal epithelial cells and stromal fibroblasts were established in culture. Cells were exposed to UVR (0, 50, 100, 150, 300, 600, 1200 J/m2). Twenty–four hours later, cells and culture medium were collected and MMP activity was determined by gelatin zymography. Results: In mono–cultures of corneal epithelial cells, 50 – 300 J/m2 UVR increased the activity of cell–associated and secreted MMP–9. MMP–2 levels increased at 600 J/m2. In mono–cultures of corneal stromal cells, low levels of UVR (50–150 J/m2) enhanced the activity of MMP–9, while higher doses of UVR (300–1200 J/m2) led to a decrease in MMP–9 activity. Production of MMP–2 did not change at any UVR level. Cultures containing approximately equal numbers of canine corneal epithelial cells and stromal cells behaved like cultures of stromal fibroblasts, showing increased MMP–9 activity at low doses of UVR and decreased MMP–9 activity upon exposure to high doses of UVR. MMP–2 production in mixed cultures showed the same pattern as stromal cultures. Differences between corneal epithelial cells and fibroblasts in induction of MMP–9 activity in response to higher doses of UVR may be related to differential susceptibility of the two cell types to UVR cytotoxicity. Conclusions: This study demonstrates that MMP–9 activity is increased in the cornea in response to UVR exposure. Unlike other MMPs, which promote corneal wound healing, MMP–9 slows the rate of corneal wound closure. These results suggest that UVR may predispose dogs and humans to persistent corneal ulceration by enhancing MMP–9 activity. We are currently investigating the pathways by which UVR induces MMP–9 activity.
This PDF is available to Subscribers Only