Effects of 17β-estradiol on the oxygen-induced retinal neovasularization in rat

Abstract

Objective To investigate the effects and mechanism of 17β-estradiol on the retinal neovasularization in rats with oxygen-induced retinopathy (OIR).Methods A total of 48 SD rats were randomly divided into control group A,control group B,experimental group A and experimental group B with 12 rats in each group.The rats in control group A and experimental group A received a hypodermic injection of 0.1 ml PBS,and the rats in control group B and experimental group B group received an a hypodermic injection of 0.1 ml 17β-estradiol.At postnatal day 7 (P7) and P14,the mRNA expression of vascular endothelial growth factor (VEGF) and Hypoxia-inducible factor (HIF) -1α in the retina were measured by real-time polymerase chain reaction (RT-PCR). At P14,endothelial cell nuclei breaking through the internal limiting membrane were counted after staining with hematoxylin and eosin (HE),and the protein expression of VEGF was measured after immunohistochemical staining.The changes of retinal ultrastructure were observed by transmission electron microscopy.Results At P14,the difference of the number of endothelial cell nuclei among four groups was statistically significant (F=10.7,P＜0.05).The number of endothelial cell nuclei in experimental group A was increased greater than that in control group A (P＜0.05) and experimental group B(q=5.16,P＜0.05).But there was no difference between control group A and experimental group B (q=0.25,P＞0.05).The difference of VEGF protein expression among the four groups was statistically significant (P＜0.05).Comparing experimental group A with control group A,B and experimental group B,the difference was statistically significant (P＜0.05).In experimental group A there was ganglion cell swelling,pale staining cytoplasm and mitochondria vacuolizationin,while these were normal in other three groups.At P7 and P14,the differences of VEGF and HIF-1 mRNA expression among four groups were statistically significant (F=14.7,16.1,13.4,17.5； P=0.001,0.005,0.003,0.009).At P7,the VEGF mRNA expression in control group B was more than that in control group A (q=5.22,P＜0.05).The VEGF mRNA expression in experimental group B was more than that in experimental group A (q=4.32,P＜0.05).At P14,the VEGF mRNA expression in control group B was more than that in control group A (q=3.72,P＜0.05),but there was no difference of HIF-1 mRNA expression between two groups.The VEGF and HIF-1 mRNA expression in experimental group B were both decreased more than those in experimental group A (q =5.12,4.08 ； P＜ 0.05).Conelusions 17β-estradiol has the effect of two-way regulation in VEGF mRNA,which increases VEGF expression in retina under hyperoxic conditions so as to develop the vascular system； which reduces VEGF and HIF-1αexpression so as to prevent pathologic neovascularization under hypoxic conditions. It provides some protection from the damage of retinal neovascularization. Key words: Retinal neovascularization/drug therapy; Estradiol; Vascular endothelial growth factors; Hypoxia-inducible factor 1, alpha subunit