Accelerated Vascular Changes of Nonproliferative Diabetic Retinopathy in a Murine Model of Diabetes

Abstract

Abstract: : Purpose: To determine whether the induction of hyperlipidemia in the insulin-resistant hyperglycemic db/db mouse enhances the development of histopathologic features of nonproliferative diabetic retinopathy. Methods: ApoE null (ApoE-/-) mice bred into the db/db background (hyperlipidemic hyperglycemic HLHG; ApoE -/- db/db) were compared with normolipidemic normoglycemic (NLNG; ApoE +/+ m/db) age-matched littermate controls. Elastase digests of the retinas of 8 normolipidemic normoglycemic (NLNG; ApoE +/+ m/db) mice were compared with the digests of 10 hyperlipidemic normoglycemic mice (HLGL; ApoE-/- db/m), 5 normolipidemic hyperglycemic mice ( NLHG; ApoE+/+ db/db) and 10 hyperlipidemic hyperglycemic mice (HLHG; ApoE-/- db/db). The specimens were analysed for the presence of pericyte ghosts, acellular capillaries and microaneurysm formation. Statistical analyses were performed using ANOVA and post-hoc tests. Results: Both acellular capillaries and pericyte ghosts were increased in HLHG (ApoE -/- db/db) mice compared to the different contorl groups as shown in the table below. Conclusion: This murine model of combined insulin-resistant diabetes and hyperlipidemia demonstrates histological findings of nonproliferative diabetic retinopathy at 6 and 8 months of age. These data suggest that induction of hyperlipidemia in diabetic mice exacerbates vascular changes of nonproliferative diabetic retinopathy.  

Keywords: animal model • diabetic retinopathy • pathology: experimental