Abstract
Purpose: :
Hyperglycemia induces retinal vasculopathy including neovascularization. The results of several studies suggest that PPARβ/Δ activation may contribute to this pathology. We have investigated the effect of hyperglycemia on retinal levels of ADRP mRNA; PPARβ/Δ is required for transcription of this gene. Additionally, we measured retinal levels of the endogenous PPARβ/Δ agonist PGI2 and VEGF protein. Our experiments were performed using the mouse model of streptozocin-induced diabetes.
Methods: :
Eight-week old C57BL/6J mice received intraperitoneal injections of streptozocin (STZ) and blood glucose levels were monitored. ADRP mRNA levels were measured by qRT-PCR using Taqman gene expression assays specific for ADRP and β-actin (normalization control). qRT-PCR data were analyzed by the comparative Ct method. VEGF protein and PGI2 were measured by ELISA.
Results: :
Three weeks after the onset of hyperglycemia (>400 mg/dl), the relative retinal ADRP expression was 2.67± 0.571 in diabetic mice and 2.39± 0.824 in the controls (p<0.05). For diabetic vs. control mice, retinal PGI2 levels were 51.8 ± 6.4 vs. 13.8± 7.3 ng/mg retinal protein (p=0.021) and retinal VEGF levels were 120.4 ± 31.8 vs. 23.9 ± 9.6 pg/mg retinal protein (p=0.044), each respectively.
Conclusions: :
These results suggest that hyperglycemia induces PPARβ/Δ activation and subsequent transcription of PPARβ/Δ target genes. The observed coordinate increase in retinal VEGF protein also suggests a functional relationship between PPARβ/Δ and VEGF-induced retinal vasculopathy.
Keywords: diabetic retinopathy • transcription factors • vascular endothelial growth factor