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Jin Zhao, Lizhong Chen, Takayuki Nagasaki; Corneal Vascularization and Loss of Homeostatic Epithelial Cell Movements. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6393.
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© ARVO (1962-2015); The Authors (2016-present)
Epithelial cells of a normal cornea exhibit steady centripetal movements whereas those of a totally vascularized cornea, such as Dstncorn1 mouse cornea and conjunctivalized cornea, are nearly stationary. This study was initiated to investigate a potential causal relationship between lack of homeostatic epithelial cell movements and vascular growth in the cornea by studying: 1) relationship between vascular growth and homeostatic epithelial cell movements in mice with a destrin gene point mutation, Dstncorn1-2J, 2) effects of reduced or lack of homeostatic epithelial cell movements on corneal neovascularization.
Ubiquitous GFP mice, Dstncorn1-2J mice, and a cross of these (GFP-Dstncorn1-2J; bred to homozygosity for both GFP expression and destrin mutation) were used. Corneal vascular growth was monitored in vivo by angiography with sulforhodamine 101. Epithelial cell movements were determined by in vivo time-lapse microscopy, tracking changes of epithelial GFP. Effects of diminished homeostatic cell movements were tested by topical application of cytoskeletal inhibitors, including colchicine, nocodazole, taxol, and cytochalasin D.
Both Dstncorn1-2J and GFP-Dstncorn1-2J corneas lacked smooth and shiny surface found in a cornea of normal strains although the cornea remained transparent. In some mice, new limbal blood vessels appeared at around 5 months of age, slowly sprouting into a peripheral zone of one or two corneal quadrants, occasionally reaching to a half the radius without a sign of opacity. By the age of 30 weeks, more than half of Dstncorn1-2J mice exhibited various degrees of corneal neovascularization. In GFP-Dstncorn1-2J corneas, some of the epithelial GFP patches in the limbus and the peripheral cornea remained stationary and failed to give rise to radial stripes, suggesting that centripetal cell movements were obstructed. This abnormality was found at as young as 12 weeks, preceding the outgrowth of new blood vessels that occurred in the vicinity. Topical colchicine application in GFP mouse corneas destroyed centripetal epithelial cell movements and triggered irreversible neovascularization.
Abnormal epithelial movements were found coincident to corneal vascular growth in aging Dstncorn1-2J mice. Colchicine inhibited homeostatic epithelial cell movements and triggered vascularization. These results are consistent with a hypothesis that loss of homeostatic epithelial cell movements are closely related to pathological vascular growth in the cornea.
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