期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 61, 期 12, 页码 -出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.61.12.20
关键词
NADPH oxidase; Nox4; corneal injury; neovascularization; corneal fibrosis
资金
- King Abdul Aziz University, Jeddah, Saudi Arabi
- Heart Foundation Postdoctoral Fellowship [PF11M6093]
- NHMRC Principal Research Fellowship
- Wiseman Trust
- National Heart Foundation of Australia [G12M6726]
- Ophthalmic Research Institute of Australia
- Eye Research Australia Foundation
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 woundhealing 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 mu L 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 TGF beta 1, 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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