Retinal and lens protective effect of sitagliptin in streptozotocin induced type-I diabetic wistar rats

Abstract

The objective of this study was to investigate effect of antidiabetic drug sitagliptin against diabetic retinopathy in wistar rats (150–180 gm). A non-diabetic group of animals received normal saline (group 1). Streptozotocin (65 mg/kg, i.p.) was administered in rats. After 15 days, rats that showed serum glucose above 200 mg/dL (diabetic) were randomly divided into following groups: group 2 (diabetic control), group 3 (sitagliptin 10 mg/kg), group 4 (sitagliptin 20 mg/kg), group 5 (sitagliptin 40 mg/kg). Serum glucose was determined periodically over a period of 90 days. Body weight and food intake of each rat was recorded during the study. Opthalmoscopic examination of the lens (slit microscopy) and retina (fundoscopy) was carried out every 7 days. Cataracted lens after the 60th day obscured the view of the retina and hence retinal damage was recorded till day 60 only. Lenticular opacities were scored under five categories (clear, stage 1, 2, 3 and 4 with stage 4 exhibiting maximum damage to the eye). On completion of 90 days, blood sugar and glycated hemoglobin was determined. Animals were then euthanized, eyes dissected and the advanced glycation end product (AGE) content of the lens was determined. Histopathology of the eye and pancreas was carried out. Animals of group 2 showed hyperglycemia, elevated glycated hemoglobin, cataract and retinal damage. Histopathology showed necrotic changes in lens. Sitagliptin showed dose dependent decrease in serum glucose, glycated hemoglobin, cataract development and retinal damage. It is concluded that, sitagliptin 40 mg/kg prolonged but not prevented the development of cataract and retinopathy in diabetic rats. Sitagliptin is effective as an ancillary drug for prolonging onset of diabetic retinopathy.