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Stage-dependent effect of pancreatic transplantation on diabetic ocular complications in the spontaneously diabetic torii rat

Background. In terms of the temporal relationship between pancreas transplantation (PTx) and reversal of diabetic ocular complications, it has been difficult but important to determine a “point of no return.” Thus, it is of great clinical interest to evaluate the efficacy of PTx on diabetic ocular complications. Methods. A spontaneous type 2 diabetic model of Spontaneously Diabetic Torii (SDT; RT1a) rats was used in the present study, and syngeneic PTx was performed. Results. In the control SDT rats that received no treatment, hyperglycemia (>250 mg/dL) was developed from 25.2±3.9 weeks of age. Lens opacity was observed in all rats at 15 weeks after the onset of diabetes. Fluorescein angiography and immunohistochemistry detected the nonperfusion area and neovascularization in the retina at 5 weeks of diabetes. Daily insulin treatment could not prevent or reverse the ocular changes in our experiment. Fluorescein filling defect of the retinal vessels was observed at 10 weeks of diabetes. However, in the PTx rats, normoglycemia was achieved at all experimental time points. Diabetic cataract and retinopathy could have been prevented and improved if PTx had been performed at 5 weeks, but not at 10 weeks after the onset of diabetes. With PTx treatment, an inhibition of angiogenesis in the retina at 5 weeks after the onset of diabetes was demonstrated by immunohistochemistry. Conclusions. Our results indicate that the potential use of the SDT rat for diabetes study and the positive effect of PTx performed before the “point of no return” could prevent and cure diabetic ocular complications.