title: NADPH oxidase 2 plays a role in experimental corneal neovascularization.
abstract: Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied. We have now analysed the role of the Nox2 isoform of NADPH oxidase in corneal neovascularization in mice following chemical injury. C57BL/6 mice aged 8-14 weeks were cauterized with an applicator coated with 75% silver nitrate and 25% potassium nitrate for 8 s. Neovascularization extending radially from limbal vessels was observed in corneal whole-mounts from cauterized wild type mice and CD31+ vessels were identified in cauterized corneal sections at day 7. In contrast, in Nox2 knockout (Nox2 KO) mice vascular endothelial growth factor-A (Vegf-A), Flt1 mRNA expression, and the extent of corneal neovascularization were all markedly reduced compared with their wild type controls. The accumulation of Iba-1+ microglia and macrophages in the cornea was significantly less in Nox2 KO than in wild type mice. In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans.
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria 3002, Australia.
authors.forename: Elsa C
authors.initials: EC
authors.lastname: Chan
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria 3002, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: van Wijngaarden
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria 3002, Australia.
authors.forename: Elsie
authors.initials: E
authors.lastname: Chan
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia.
authors.forename: Darleen
authors.initials: D
authors.lastname: Ngo
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria 3002, Australia.
authors.forename: Jiang-Hui
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia.
authors.forename: Hitesh M
authors.initials: HM
authors.lastname: Peshavariya
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria 3002, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria 3002, Australia Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria 3002, Australia guei-sheung.liu@unimelb.edu.au.
authors.forename: Guei-Sheung
authors.initials: GS
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002056:Burns / Q000201:enzymology / Q000473:pathology; D002425:Cautery; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; D042461:Vascular Endothelial Growth Factor A; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: NADPH oxidase; Nox2; VEGF; chemical cauterization; corneal neovascularization