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

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.

Ocular lamellar crystalline gels for sustained release and enhanced permeation of resveratrol against corneal neovascularization

“…VEGF is the most essential angiogenic factor responsible for the growth of new vessels. It is secreted by corneal epithelium cells and then sequestrated by the basement membrane in physiological conditions (Cakmak et al., 2018 ; Fu & Xin, 2019 ). The expression levels of VEGF in the control group were higher compared to the healthy group ( Figure 8(F,G) ), indicating that corneal alkali burns increased VEGF expression, which thereby induced CNV.…”

Melatonin exerts anti-angiogenic and anti-inflammatory effects in alkali-burned corneas

“…At 7 days after alkali injury, the right eyes were harvested and fixed in 10% neutral buffered formalin overnight, then embedded in paraffin. Each eye was cut into 5 μm vertical sections through the corneal central area and stained with hematoxylin and eosin (H&E) according to standard techniques (31). Histopathologic analyses of corneal tissues were performed under a microscope (Carl Zeiss LSM 510, Germany) to detect inflammatory cells and central corneal thickness.…”

Hypoxia adaptation in the cornea: Current animal models and underlying mechanisms

“…Hif1α by shRNA attenuated the corneal angiogenesis both in a contact lens wearing mouse and a rabbit alkali burn model. 60 Intervening the combination between Hif1α/Hif2α and Hifβ by acriflavine treatment decreased the neovascularization during the clinical disease period. 6,61 However, inhibition of HIF-1α did not reduce the VEGF level in the bovine corneal stromal cells under hypoxic culture conditions.…”

“…The HIF‐1α signaling pathway was found to play a critical role in regulating VEGF expression in corneal neovascularization, which is a sight‐threatening condition caused by new vessel formation from the limbus and its invasion into the cornea. Silencing Hif1α by shRNA attenuated the corneal angiogenesis both in a contact lens wearing mouse and a rabbit alkali burn model 60 . Intervening the combination between Hif1α/Hif2α and Hifβ by acriflavine treatment decreased the neovascularization during the clinical disease period 6,61 .…”