Abstract

Severe corneal inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. In this study, we used the cornea to examine the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, methanol (Met) and hexane (Hex), from the seed of Cucurbita argyrosperma, on inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. We evaluated: opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological changes. Also, we assessed the inflammatory (cyclooxigenase-2, nuclear factor-kappaB, and interleukin-1β) and angiogenic (vascular endothelial growth factor A, VEGF-A; -receptor 1, VEGFR1; and -receptor 2, VEGFR2) markers. Levels of Cox-2, Il-1β, and Vegf-a mRNA were also determined. After treatment, we observed a reduction in corneal edema, with lower opacity scores and cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased the CNV area. The staining of inflammatory and angiogenic factors was significantly decreased and related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed has the potential to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.

Highlights

  • Angiogenesis, inflammation, and oxidative stress are important factors that predispose to and promote the progression of degenerative diseases, and corneal diseases are not an exception

  • Signaling pathway in inflammatory, epithelial, and endothelial cells is a key step for the transcriptional overexpression of pro-inflammatory and proangiogenic factors, including interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor A (VEGF-A)

  • The corneais is a transparent, avascular, and immune-privileged tissue. the the response and growth of new vessels induced by infections, autoimmunity, and chemical burns may cause inflammatory response and growth of new vessels induced by infections, autoimmunity, and chemical burns may cause vision loss and a high rejection rate of corneal allografts if not treated effectively [1,25]

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Summary

Introduction

Angiogenesis, inflammation, and oxidative stress are important factors that predispose to and promote the progression of degenerative diseases, and corneal diseases are not an exception. CNV is associated with a high rate of corneal allograft rejection [1]. In this context, the nuclear factor-kappaB (NF-κB). Signaling pathway in inflammatory, epithelial, and endothelial cells is a key step for the transcriptional overexpression of pro-inflammatory and proangiogenic factors, including interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor A (VEGF-A). Interleukin-1β, IL-6, and tumor necrosis factor alpha (TNF-α) regulate COX-2; they are overexpressed during inflammation [2,3,4]

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