Inhibited corneal neovascularization in rabbits following corneal alkali burn by double-target interference for VEGF and HIF-1α.

Zhi-Ming Xin,Ying-Cong Fu

doi:10.1042/bsr20180552

Abstract

Expression of hypoxia-inducible factor (HIF) 1α has been observed in corneal neovascularization (CNV). Vascular endothelial growth factor (VEGF), one of the most well-known angiogenic factors in CNV, is under the regulation of HIF-1. The present study aims to investigate the synergistic effects of VEGF and HIF-1α gene silencing on alkali burn-induced CNV in rabbits. The models of rabbits in corneal alkali burn were established. SiRNA recombinant adenovirus was used to explore the synergistic effects of VEGF and HIF-1α gene silencing on alkali burn-induced CNV. CNV area and ultrastructure of cornea were observed. The expression of VEGF and HIF-1α was detected. CNV was observed in rabbits following alkali burn. In addition, overexpressed VEGF and HIF-1α was also observed in rabbits following alkali burn. Then, silencing HIF-1α or silencing VEGF decreased area of CNV, inhibited neovascularization and improved pathological changes, while double-target interference for VEGF and HIF-1α decreased area of CNV inhibited neovascularization, and improved pathological changes to a greater extent. Our study provides evidences emphasizing the distinct notion that VEGF and HIF-1α play the contributory role in alkali burn-induced CNV as a result of double-target interference for VEGF and HIF-1α inhibiting CNV in rabbits following corneal alkali burn.

Highlights

Normal cornea is transparent and free of blood vessels, and corneal avascularity is critical for optical clarity and maintenance of vision [1]
There was no marked difference of the corneas of rabbits between the hypoxia-inducible factor (HIF)-1α siRNA and vascular endothelial growth factor (VEGF) siRNA groups, in which a large area of semitransparency and local corneal edema existed and a relatively large amount of new vessels extended into the corneal graft
The results of comparisons amongst six groups showed that the area containing Corneal neovascularization (CNV) in the normal control group was the lowest at every time point and in the HIF-1α-VEGF siRNA group was the second lowest, indicating significant difference (P

Summary

Introduction

Normal cornea is transparent and free of blood vessels, and corneal avascularity is critical for optical clarity and maintenance of vision [1]. Alkali burn is regarded as one of the most serious contributors of CNV and may cause severe injury to the cornea and vision [6]. Some treatments, such as laser photocoagulation, medication, and surgery, are applied for the treatment of CNV diseases, but recently, no clear consensus has been reached on the most efficacious treatment option for CNV, which indicates that novel treatments for CNV diseases are in urgent need [7,8]

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