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

• Published in: Investigative ophthalmology & visual science Vol. 50; no. 10; pp. 4761 - 4768
• Main Authors: Lu, Peirong, Li, Longbiao, Liu, Gaoqin, Zhang, Xueguang, Mukaida, Naofumi
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.10.2009; Association for Research in Vision and Ophtalmology
• Subjects: Animals; Antigens, Differentiation; Biological and medical sciences; Burns, Chemical - etiology; Cornea - drug effects; Corneal Neovascularization - etiology; Corneal Neovascularization - metabolism; Disease Models, Animal; Eye and associated structures. Visual pathways and centers. Vision; Eye Burns - chemically induced; Fluorescent Antibody Technique, Indirect; Fundamental and applied biological sciences. Psychology; Interleukin 1 Receptor Antagonist Protein - physiology; Interleukin-1alpha - metabolism; Interleukin-1beta - metabolism; Macrophages - physiology; Macrophages, Peritoneal - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Knockout; Neutrophils - physiology; Nitric Oxide Synthase Type II - metabolism; Ophthalmology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Sodium Hydroxide - toxicity; Vascular Endothelial Growth Factor A - metabolism; Vertebrates: nervous system and sense organs; Cornea; Angiogenic factor; Anomaly; Antagonist; Neovascularization; Ophthalmology; Experimental study
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.08-2732

To address the roles of the endogenously produced IL-1ra in the course of corneal neovascularization (CNV). 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. 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. IL-1ra KO exhibited enhanced alkali-induced CNV through enhanced intracorneal macrophage infiltration and increased expression of VEGF and iNOS.