Wound Healing After Alkali Burn Injury of the Cornea Involves Nox4-Type NADPH Oxidase

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Hakami, NY; Dusting, GJ; Chan, EC; Shah, MH; Peshavariya, HMDate
2020-10-01Source Title
Investigative Ophthalmology and Visual SciencePublisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INCAffiliation
Surgery (St Vincent's)Ophthalmology (Eye & Ear Hospital)
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Hakami, N. Y., Dusting, G. J., Chan, E. C., Shah, M. H. & Peshavariya, H. M. (2020). Wound Healing After Alkali Burn Injury of the Cornea Involves Nox4-Type NADPH Oxidase. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 61 (12), https://doi.org/10.1167/iovs.61.12.20.Access Status
Open AccessOpen Access at PMC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585390Abstract
Purpose: Corneal injury that occurs after burning with alkali initiates wound-healing processes, including inflammation, neovascularization, and fibrosis. Excessive reactions to injury can reduce corneal transparency and thereby compromise vision. The NADPH oxidase (Nox) enzyme complex is known to be involved in cell signaling for wound-healing angiogenesis, but its role in corneal neovascularization has been little studied. Methods: The center corneas of wild-type and Nox4 knockout (KO) mice were injured with 3 µL 1 M NaOH, while the contralateral corneas remained untouched. On day 7, mRNA expression levels of NADPH oxidase isoforms, the proangiogenic factors VEGF-A and TGFβ1, and proinflammatory genes ICAM-1 and VCAM-1 were determined. Corneal neovascularization and fibrosis were visualized using PECAM-1 antibody and picrosirius red staining, respectively, on the same day. Results: Expressions of both Nox2 and Nox4 gene isoforms as well as the above genes were markedly increased in the injured corneas at 7 days. Injured corneas showed neovascularization and fibrosis as well as an increase in clinical opacity score. All responses stimulated by alkali burn were abrogated in Nox4 KO mice. Conclusions: Nox4 could be a new target to treat pathologic corneal wound-healing responses and such targeting might prevent blindness caused by burn injuries.
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