HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: iovs.08-2732v1 50/10/4761    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lu, P. Articles by Mukaida, N. Search for Related Content PubMed PubMed Citation Articles by Lu, P. Articles by Mukaida, N.

Enhanced Experimental Corneal Neovascularization along with Aberrant Angiogenic Factor Expression in the Absence of IL-1 Receptor Antagonist

¹From the Department of Ophthalmology and the ²Clinical Immunology Key Laboratory of Jiangsu Province, the First Affiliated Hospital of Soochow University, Suzhou, China PR; and the ³Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Japan.

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, and IL-1β 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 and IL-1β 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.