Corneal epithelium wound healing and chronological change of cornea in a spontaneous type 2 diabetes model rat

Abstract

Purpose: We previously reported that in Spontaneously Diabetic Torii (SDT) rats, diabetic cataracts were observed before 40 weeks of age, diabetic retinopathy was observed after 50 weeks of age, and that rubeotic glaucoma was observed after 77 weeks of age. This study tested the hypothesis that the SDT spontaneous type 2 diabetes model rat also develops diabetic keratopathy.

Methods: The subjects of this study were 10 SDT rats, and 10 Sparague-Dawley (SD) rats were used as control. Corneas were observed by surgical microscope. Corneal sensitivity was measured by Cochet-Bonnet esthesiometer, and tear secretion volume by phenol red thread tear test regularly from 8 weeks of age to 65 weeks of age. We compared corneal epithelium wound healing after 50 weeks of age (n=6). Expressions of MMP9 and F4/80 were examined immunohistologically at 65 weeks of age (n=4). Student’s t-test was used for statistical analysis.

Results: During the follow up period, no corneal abnormality was observed in SDT and control rats. Change of corneal sensitivity was also not observed in SDT and control. Tear secretion volume in SDT was larger than control at 61 weeks of age, but no significant difference was observed at the other timings. MMP9 was strongly expressed in the corneal epithelium in 4 of 4 SDT rats, and weakly in 3 of 4 control rats. F4/80 was expressed in corneal epithelium and stroma in 4 of 4 SDT rats and 2 of 4 control rats. Corneal wound healing rates were 40±22% in SDT and 62±13% in control after 24 hours, 70±12% in SDT and 90±16% in control after 48 hours, and 84±12% in SDT and 93±10% in control after 72 hours, indicating that SDT rats had significantly slower corneal wound healing than control (p=0.01、0.01、0.02).

Conclusions: Corneal sensitivity and tear secretion did not change in SDT rat before 65 weeks of age, but the existence of subclinical inflammation was suggested histologically. Corneal wound healing was prolonged in SDT rats after 50 weeks of age, and the onset of diabetic keratopathy was suggested.