Enhanced experimental corneal neovascularization along with aberrant angiogenic factor expression in the absence of IL-1 receptor antagonist.
نویسندگان
چکیده
PURPOSE To address the roles of the endogenously produced IL-1ra in the course of corneal neovascularization (CNV). METHODS CNV was induced by alkali injury and compared in wild-type (WT), IL-1 receptor antagonist (ra) knockout (KO) mice and anti-IL-1ra antibody-treated WT mice 2 weeks after injury. Angiogenic factor expression and leukocyte accumulation in the early phase after injury were quantified by RT-PCR and immunohistochemical analysis, respectively. RESULTS The mRNA expression of IL-1ra, IL-1 alpha, and IL-1beta was augmented, together with infiltration of F4/80(+) macrophages and Gr-1(+) neutrophils, in corneas after alkali injury. Intracorneally infiltrating macrophages, but not neutrophils, expressed IL-1ra. Compared with WT mice, either IL-1ra KO mice or anti-IL-1ra antibody-treated WT mice exhibited enhanced CNV 2 weeks after injury, as evidenced by enlarged CD31(+) areas. Concomitantly, the infiltration of F4/80(+) macrophages was more significantly enhanced in IL-1ra KO mice than in WT mice. Intraocular mRNA expression enhancement of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) was greater in IL-1ra KO mice than in WT mice after injury. Moreover, IL-1 alpha and IL-1 beta enhanced VEGF and iNOS expression by murine peritoneal macrophages. CONCLUSIONS IL-1ra KO exhibited enhanced alkali-induced CNV through enhanced intracorneal macrophage infiltration and increased expression of VEGF and iNOS.
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ورودعنوان ژورنال:
- Investigative ophthalmology & visual science
دوره 50 10 شماره
صفحات -
تاریخ انتشار 2009