Vitreous Fluid of db/db Mice Exhibits Alterations in Angiogenic and Metabolic Factors Consistent with Early Diabetic Retinopathy

Abstract

Background: This study evaluated the postulate that the vitreous of diabetic db/db mice, a genetic model of type 2 diabetes that manifests hyperglycemia and insulin resistance, exhibits alterations in angiogenic and metabolic factors that reflect abnormalities in the retinal microvasculature participatory in the pathogenesis of diabetic retinopathy. Methods: Vitreous obtained from db/db and age-matched nondiabetic db/m mice was analyzed by Western blot for pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF), by immunoassay for type IV collagen, and by measurement of TBARs for lipid peroxide products. Results: Compared to nondiabetic db/m controls, vitreous from db/db mice contained decreased PEDF and increased VEGF (VEGF:PEDF relative ratio 2.2 ± 0.3 and 1.0 ± 0.1 in db/db vs. db/m, respectively; p < 0.05), and elevated concentrations of lipid peroxide products (187 ± 43 and 84 ± 15 ng/ml in db/db vs. db/m, respectively; p < 0.05) and type IV collagen (5.2 ± 0.7 and 3.1 ± 0.4 nmol/ml in db/db vs. db/m, respectively; p < 0.05). These changes were observed at age 18–20 weeks, consistent with an early stage in the development of retinal microvascular pathology. Conclusions: The findings support the potential usefulness of vitreous from the db/db mouse as a model tissue for investigation of pathogenetic factors and assessment of therapeutic interventions in early diabetic retinopathy.