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Wei-Ting Ho, I-Jong Wang; Matrix metalloproteinase inhibitor reverses endothelial-mesenchymal transformation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1168.
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© ARVO (1962-2015); The Authors (2016-present)
Ex vivo culture of human corneal endothelial cells is often subjected to gradual mesenchymal transformation and loss of function. The present study was conducted to demonstrated the effect of matrix metalloproteinase inhibitor (MMPI) in reversing endothelial-mesenchymal transformation (EnMT) during ex vivo culture and in vivo.
Bovine corneal endothelial cells (BCECs) were cultured in medium with or without MMPI. Cell shape and protein localization were shown by immunofluorescence. MMP activity was monitored by fluorogenic substrate cleavage assay. Real-time PCR was used to determine RNA expression, and protein level was determined by Western blot. To determine the EnMT-reversing effect of MMPI in vivo, rat corneal endothelium cryo-injury model was used. Subsequent ultrasound biomicroscopy and histological examination were performed to evaluate corneal thickness. <br />
During ex vivo culture, BCECs underwent EnMT and had upregulated MMP expression. Addition of MMPI to cultured BCECs decreased the level of EMT regulators, snail and slug. The phosphorylation and degradation of active beta-catenin was also accelerated after MMPI, which may result from decreased N-cadherin shedding and increased N-cadherin level on the cell membrane. In rat corneal endothelium cryo-injury model, intracameral injection of MMPI reversed EnMT and resulted in less corneal edema.<br />
MMPI can reverse EnMT and preserve the function of corneal endothelial cell both during ex vivo expansion and in vivo. This may offer a therapeutic target in regenerative medicine for the treatment of corneal endothelial dysfunctions.
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