title: Involvement of NADPH oxidases in alkali burn-induced corneal injury.
abstract: Chemical burns are a major cause of corneal injury. Oxidative stress, inflammatory responses and neovascularization after the chemical burn aggravate corneal damage, and lead to loss of vision. Although NADPH oxidases (Noxs) play a crucial role in the production of reactive oxygen species (ROS), the role of Noxs in chemical burn-induced corneal injury remains to be elucidated. In the present study, the transcription and expression of Noxs in corneas were examined by RT-qPCR, western blot analysis and immunofluorescence staining. It was found that alkali burns markedly upregulated the transcription and expression of Nox2 and Nox4 in human or mouse corneas. The inhibition of Noxs by diphenyleneiodonium (DPI) or apocynin (Apo) effectively attenuated alkali burn-induced ROS production and decreased 3-nitrotyrosine (3-NT) protein levels in the corneas. In addition, Noxs/CD11b double‑immunofluorescence staining indicated that Nox2 and Nox4 were partially co-localized with CD11b. DPI or Apo prevented the infiltration of CD11b-positive inflammatory cells, and inhibited the transcription of inflammatory cytokines following alkali burn-induced corneal injury. In our mouse model of alkali burn-induced corneal injury, corneal neovascularization (CNV) occurred on day 3, and it affected 50% of the whole area of the cornea on day 7, and on day 14, CNV coverage of the cornea reached maximum levels. DPI or Apo effectively attenuated alkali burn‑induced CNV and decreased the mRNA levels of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptors and matrix metalloproteinases (MMPs). Taken together, our data indicate that Noxs play a role in alkali burn-induced corneal injury by regulating oxidative stress, inflammatory responses and CNV, and we thus suggest that Noxs are a potential therapeutic target in the future treatment of chemical-induced corneal injury.
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Gu
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Xu
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Han
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qiu-Ping
authors.initials: QP
authors.lastname: Liu
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jing-Lin
authors.initials: JL
authors.lastname: Yi
authors.affiliation: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jing-Ming
authors.initials: JM
authors.lastname: Li
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000468:Alkalies; D000818:Animals; D002057:Burns, Chemical / Q000150:complications / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D065306:Corneal Injuries / Q000150:complications / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D016510:Corneal Neovascularization / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005126:Eye Burns / Q000150:complications / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000098:Acetophenones; D000468:Alkalies; D004791:Enzyme Inhibitors; D009861:Onium Compounds; C007517:diphenyleneiodonium; C056165:acetovanillone; D019255:NADPH Oxidases