Volume 29, Issue 5, 2020
DOI: 10.24205/03276716.2020.1074
Roles of Hypoxia-Inducible Factor-1α And Vascular Endothelial Growth Factor in Neovascularization Upon Proliferative Diabetic Retinopathy
Abstract
Objective: To observe the expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in fibrovascular membrane from patients with proliferative diabetic retinopathy (PDR) and epiretinal membrane from non-diabetic patients with idiopathic macular epiretinal membrane, and to preliminarily explore the roles of HIF-1α and VEGF in neovascularization in the case of PDR.
Methods: A total of 60 patients (60 eyes) diagnosed as type 2 PDR in our hospital from September 2018 to September 2019, who needed to receive 23G pars plana vitrectomy (PPV), were included in this study, and 20 patients diagnosed as macular hole were selected as controls. Experimental group was further divided into two subgroups, i.e. group A (n=30, non-injected PDR group, directly treated with vitrectomy) and group B (n=30, injected PDR group, intravitreally injected with anti-VEGF drug ranibizumab before operation). Pathological specimens of the fibrovascular membrane in PDR and macular epiretinal membrane were obtained during PPV. Immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) were applied to detect the expressions of HIF-1α, VEGF and VEGF receptor 2 (VEGFR2), and the correlation between two variables was analyzed using Spearman’s method.
Results: Immunohistochemical staining showed that the protein expressions of HIF-1α, VEGF and VEGFR2 in the fibrovascular membrane were all positive in experimental group, and they were significantly higher in injected PDR group than those in non-injected PDR group (P<0.05). RT-PCR exhibited that the mRNA expressions of HIF-1α and VEGF were the highest in non-injected PDR group and the lowest in control group. There were statistically significant differences in the relative mRNA expression levels of HIF-1α and VEGF in the pathological specimens of fibrovascular membrane and macular epiretinal membrane among control group, injected PDR group and non-injected PDR group (P<0.05) as well as between injected PDR group and non-injected PDR group (P<0.05). Spearman’s analysis revealed that the expression of VEGFR2 was significantly positively correlated with those of HIF-1α and VEGF (P<0.05).
Conclusion: HIF-1α, VEGF and VEGFR2 are highly expressed in the fibrovascular membrane from PDR patients, and the VEGF signaling pathway may participate in the formation and development of new vessels in the case of PDR
Keywords
hypoxia-inducible factor-1α; vascular endothelial growth factor; neovascularization; proliferative diabetic retinopathy