Delayed wound closure and phenotypic changes in corneal epithelium of the spontaneously diabetic Goto-Kakizaki rat

PURPOSE: To characterize wound closure and phenotypic changes in the corneal epithelium of the Goto-Kakizaki (GK) rat, a spontaneous model of type 2 diabetes. METHODS: Corneal wound healing was monitored by fluorescein staining after epithelial debridement. Tear secretion was measured with the Schirmer test, and corneal sensation was evaluated with an esthesiometer in 13- to 15-week-old GK and Wistar (control) rats. The distributions of cytokeratin 12 (K12), K14, and connexin43 in the corneal epithelium were examined by immunohistofluorescence analysis. The proliferation capacity of epithelial cells in the intact cornea and during wound healing was evaluated by immunostaining for Ki-67. RESULTS: Tear secretion, corneal sensation, and corneal epithelial wound closure rate were all decreased in GK rats compared with those in Wistar rats. Whereas connexin43, K14, and Ki-67 were all restricted to the single layer of basal cells in the corneal epithelium of Wistar rats, they were detected in the two layers of cells closest to the basement membrane in that of GK rats. The frequency of Ki-67-positive cells in the intact corneal epithelium was greater in GK rats than in Wistar rats, and it was increased to a greater extent in the peripheral cornea of GK rats than in that of Wistar rats during wound healing. CONCLUSIONS: Spontaneously diabetic GK rats manifest characteristics similar to those of diabetic keratopathy in humans, including delayed wound closure, and they exhibit phenotypic changes in corneal epithelial cells.