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Jin Zhao, Lizhong Chen, Takayuki Nagasaki; Corneal Vascular Regression by Forced Epithelial Cell Movements. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2403.
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We found previously that loss of homeostatic epithelial cell movements was closely related to pathological vascular growth in the cornea, and we hypothesized that there is a causal relationship between them. We tested the hypothesis by examining: 1) if cell motility inhibitors cause corneal neovascularization, and 2) if restoration of centripetal epithelial cell movements triggers regression of established central corneal blood vessels.
Ubiquitous GFP mice, Dstncorn1, and a cross of these (GFP-Dstncorn1) were used. To impede homeostatic cell movements, cytoskeletal inhibitors including cytochalasin D, taxol and ML-9 were applied topically. In Dstncorn1 mice where corneal epithelial cells were stationary, centripetal cell movements were created by repeated mechanical scraping of central epithelium twice a week. Epithelial cell movements were determined by in vivo time-lapse microscopy, tracking changes of epithelial GFP. Corneal vascular growth was monitored in vivo by angiography with sulforhodamine 101.
Similar to what we found previously with colchicine, topical taxol application abolished centripetal epithelial cell movements and triggered irreversible neovascularization. After ML-9 application, some corneas developed peripheral new vessels that regressed later on, and others developed blood vessels that reached the center. Cytochalasin D also triggered vascularization, but the effect was reversible when the drug treatment was stopped. In an adult Dstncorn1 mouse cornea, epithelial cells are generally immobile and central corneal vasculature was stable. Repeated central epithelial scraping in these eyes forced cells to move centripetally, and as a consequence radial epithelial GFP stripes were observed. Coincidentally, central corneal vessels regressed completely within two weeks, and the central cornea remained free from blood vessels for at least a month, some for more than two months. Central vessels grew back soon after restoration of stationary epithelium by way of stopping the epithelial scraping. In a small number of eyes, epithelium failed to heal properly within a few days after epithelial scraping, thus failing to trigger constant cell movements; robust vascular regression was not obvious in these eyes.
Some cell motility inhibitors triggered corneal vascularization in a normal eye. Forced epithelial cell movements triggered regression of vasculature in the central cornea of Dstncorn1 mice. These results are consistent with a hypothesis that loss of homeostatic epithelial cell movements is a cause of pathological vascular growth in the cornea.
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