Enhanced experimental corneal neovascularization along with aberrant angiogenic factor expression in the absence of IL-1 receptor antagonist.
OBJECTIVE
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.
Lu
Peirong
P
Department of Ophthalmology, First Affiliated Hospital of Soochow University, Suzhou, PR China. lupeirong@yahoo.com.hk
Li
Longbiao
L
Liu
Gaoqin
G
Zhang
Xueguang
X
Mukaida
Naofumi
N
D000818:Animals; D000943:Antigens, Differentiation; D002057:Burns, Chemical / Q000209:etiology; D003315:Cornea / Q000187:drug effects; D016510:Corneal Neovascularization / Q000209:etiology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005126:Eye Burns / Q000139:chemically induced; D019084:Fluorescent Antibody Technique, Indirect; D053590:Interleukin 1 Receptor Antagonist Protein / Q000502:physiology*; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012972:Sodium Hydroxide / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000943:Antigens, Differentiation; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C036763:monocyte-macrophage differentiation antigen; C467480:vascular endothelial growth factor A, mouse; D012972:Sodium Hydroxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse