Abstract

Background/Aims: The Spontaneously Diabetic Torii (SDT) rat develops advanced diabetic retinopathy (DR). The aim of this study was to identify advanced glycation end products (AGEs) related to vascular endothelial growth factor (VEGF) expression, a cause of DR in SDT rats. Methods: One eye was obtained from six SDT rats (blood glucose, >250 mg/dl) and 10 nondiabetic normal Sprague- Dawley (SD) rats and prepared for immunohistochemical study of VEGF and AGEs (pyrraline, pentosidine, carboxy methyl lysine (CML)). Immunostaining was described as minimal, moderate, and severe. Results: In diabetic rats, for CML, five eyes had severe and one moderate immunostaining. For pyrraline, one eye had moderate and five eyes minimal immunostaining. For pentosidine, one eye had moderate and five eyes minimal immunostaining. For VEGF, three eyes each had moderate and severe immunostaining. In nondiabetic rats, for CML one eye had minimal, seven had moderate, and two had severe immunostaining. For pyrraline, four eyes had moderate and six eyes minimal immunostaining. For pentosidine, 10 eyes had minimal immunostaining. For VEGF, one eye had moderate and nine had minimal immunostaining. The prevalence rates of CML and VEGF were significantly (P<0.05, P<0.001, respectively) greater in diabetic than in nondiabetic rats. The prevalence rates of pyrraline and pentosidine were not significantly (P=0.35, P=0.38) different between diabetic and nondiabetic rats. Conclusion: CML coexists with VEGF and may be involved in the pathogenesis of severe ocular complications in SDT rats.

Highlights

  • Diabetic ocular complications, such as diabetic retinopathy (DR), cataracts, and rubeotic glaucoma, impair vision and quality of life

  • We evaluated the grade of the immunostaining in each sample without knowing whether the eye was obtained from a SD or Spontaneously Diabetic Torii (SDT) rat

  • The prevalence rates of immunoreactivity for CML and vascular endothelial growth factor (VEGF) were significantly greater in the retinas of diabetic rats than in nondiabetic rats (P

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Summary

Introduction

Diabetic ocular complications, such as diabetic retinopathy (DR), cataracts, and rubeotic glaucoma, impair vision and quality of life. Vascular endothelial growth factor (VEGF), an important cytokine that induces proliferative DR [4,5], is correlated with several metabolic changes, including increased polyol pathway activity [6,7,8,9], activation of protein kinase C (PKC) [10,11,12,13,14], increased oxidative stress [13,15,16], and accumulation of advanced glycation end products (AGEs) [13,17,18,19] These induce retinal vascular dysfunction and retinal ischemia.

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