| First Author | Lu P | Year | 2012 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 53 |
| Issue | 7 | Pages | 3516-26 |
| PubMed ID | 22570350 | Mgi Jnum | J:196811 |
| Mgi Id | MGI:5489972 | Doi | 10.1167/iovs.10-5548 |
| Citation | Lu P, et al. (2012) Critical role of TNF-alpha-induced macrophage VEGF and iNOS production in the experimental corneal neovascularization. Invest Ophthalmol Vis Sci 53(7):3516-26 |
| abstractText | PURPOSE: We evaluated the roles of tumor necrosis factor (TNF)-alpha 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-alpha antagonist and recombinant TNF-alpha. 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-alpha 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-alpha enhanced VEGF and iNOS expression by peritoneal macrophage from WT, but not KO mice. Topical application of TNF-alpha antagonist reduced CNV, while topical application of recombinant TNF-alpha enhanced it. CONCLUSIONS: TNF-Rp55-KO mice exhibited impaired alkali-induced CNV through reduced intracorneal infiltrating macrophage VEGF and iNOS expression. |
