Effects of HIF-1α on diabetic retinopathy angiogenesis and VEGF expression

OBJECTIVE: To investigate the effect of hypoxia inducing factor (HIF)-1 alpha on the expression of vascular endothelial growth factor (VEGF) and angiogenesis in diabetic retinopathy. PATIENTS AND METHODS: 8-week healthy SD rats were used for the experiments. Under systemic anesthesia condition, control rats received a saline injection into the left ocular body (control A group), and 2 mu l antisense oligonucleotides (ASODN) (10 mu mol/L) into right eye (control B group). Model rats received a saline injection into the left eye (model A group), and 2 mu l ASODN (10 mu mol/L) into the right eye (model B group). Rats received an intraocular injection of HIF-1 alpha ASODN for 2, 4, and 6 weeks (A1, A2. A3, B1, B2, B3, respectively). Retinal vessel development was observed by ADP staining. Vascular endothelial cells penetrating retinal inner membrane were counted. Immunohistochemistry was used to detect expressions of VEGF and HIF-1 alpha proteins in the retina. RESULTS: Prominent angiogenesis and hyperplasia were found in model A group. Relatively fewer newly formed vessels were shown in model group B. However, no significant change of retinal vascular morphology was presented in control group. Of note, the vascular endothelial cell counts, VEGF and HIF-1 alpha contents were significantly increased in model group (p < 0.05). After treatment with HIF-1 alpha ASODN, lower endothelial cell counts was found in model B group (p < 0.05 comparing to model A). VEGF expression in model B group was significantly decreased, among which, model B3 was observed with lower cell counts than model B1 or B2 (p < 0.05 comparing to model A). Injection of HIF-1 alpha ASODN significantly suppressed HIF-1 alpha level in model B in a time-dependent manner. CONCLUSIONS: Retinal angiogenesis is closely related with increasing level of HIF-1 alpha. Inhibition of HIF-1 alpha suppressed VEGF expression and deterred angiogenesis in a time-dependent manner. This provided novel insights for treating diabetic retinopathy.