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(Investigative Ophthalmology and Visual Science. 2002;43:955-962.)
© 2002 by The Association for Research in Vision and Ophthalmology, Inc.

Expression of Integrins and MMPs during Alkaline-Burn-Induced Corneal Angiogenesis

Heying Zhang1, Chen Li2 and Peter C. Baciu2

1 From Medimmune, Gaithersburg, Maryland; and 2 Allergan, Inc., Irvine, California.

PURPOSE. To determine in a corneal alkaline burn model of angiogenesis whether the expression of integrins and MMPs is consistent with a VEGF-induced angiogenic response.

METHODS. Neovascularization in female Sprague-Dawley rats was induced by alkaline cauterization of the central cornea. RT-PCR for integrins {alpha}1, {alpha}2, ß3, and ß5; the endothelial marker CD31; and metalloproteinases MMP-2 and MT1-MMP was performed on naive corneas and on cauterized corneas 72 and 288 hours after cautery. Analyses of protein and MMP expression were conducted on naive corneas and on cauterized corneas 24, 72, 120, and 168 hours after cautery by immunofluorescence microscopy and gelatin zymography.

RESULTS. RT-PCR indicated a correlation between the induced angiogenic response and the expression of {alpha}1 and ß3 integrin subunits and MT1-MMP. Immunohistochemical analysis indicated that {alpha}1, {alpha}2, {alpha}5, and ß5 integrins and MMP-2 and MT1-MMP were expressed on the newly developing vasculature. The ß3 integrin was preferentially expressed on platelets.

CONCLUSIONS. Integrin expression during neovascularization of rat corneas in response to alkaline injury correlates with an angiogenic response that uses the VEGF/{alpha}vß5 pathway. MMP-2 and MT1-MMP, but not MMP-9, are expressed in a pattern consistent with their involvement in the angiogenic response.




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