Abstract:
PURPOSE:We evaluated the roles of tumor necrosis factor (TNF)-α in alkali-induced corneal neovascularization (CNV). METHODS:CNV was induced by alkali injury and compared in wild-type (WT) BALB/c mice, and TNF receptor 1-deficient (TNF-Rp55 KO) counterparts, or in mice treated with TNF-α antagonist and recombinant TNF-α. Angiogenic factor expression and leukocyte accumulation in the early phase after injury were quantified by real-time PCR and immunohistochemical analysis, respectively. RESULTS:Alkali injury augmented the intraocular mRNA expression of TNF-α and its receptor, together with a transient macrophage and neutrophil infiltration. Compared to WT mice, TNF-Rp55 KO mice exhibited reduced CNV. Intraocular F4/80-positive macrophages and Ly-6G-positive neutrophils infiltration did not change in KO mice compared to WT mice after the injury. Alkali injury induced a massively increased intraocular mRNA expression of angiogenic factors, including vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), interleukin (IL)-6, E-selectin, and intercellular adhesion molecule (ICAM)-1 in WT mice, whereas these increments were retarded severely in KO mice. Immunofluorescence analysis demonstrated that F4/80-positive cells expressed VEGF and iNOS. Moreover, TNF-α enhanced VEGF and iNOS expression by peritoneal macrophage from WT, but not KO mice. Topical application of TNF-α antagonist reduced CNV, while topical application of recombinant TNF-α enhanced it. CONCLUSIONS:TNF-Rp55-KO mice exhibited impaired alkali-induced CNV through reduced intracorneal infiltrating macrophage VEGF and iNOS expression.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Lu P,Li L,Liu G,Baba T,Ishida Y,Nosaka M,Kondo T,Zhang X,Mukaida Ndoi
10.1167/iovs.10-5548subject
Has Abstractpub_date
2012-06-14 00:00:00pages
3516-26issue
7eissn
0146-0404issn
1552-5783pii
iovs.10-5548journal_volume
53pub_type
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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