title: Interleukin-18 regulates pathological intraocular neovascularization.
abstract: Recently, the proinflammatory cytokine IL-18 has been shown to have a role in angiogenesis. This study aimed to elucidate its role in abnormal neovascularization (NV) in an oxygen-induced retinopathy (OIR) mouse model of the retinopathy seen in human premature newborns. IL-18 was constitutively expressed in the retina in C57BL/6 mice, but expression transiently dropped on Day 17 after birth in mice exposed to 75% oxygen for 5 days between Days 7 and 12. Coincident with the IL-18 reduction in oxygen-treated mice, vascular endothelial growth factor was expressed in the retina, and OIR developed. By Day 24, NV in the retina had regressed to normal levels. By contrast, IL-18 knockout mice, exposed to elevated oxygen concentrations, developed more severe OIR on Day 17, and it is important that this persisted until Day 24. This suggested that IL-18 negatively regulated retinal NV. To investigate this further, we administrated recombinant IL-18 to C57BL/6 mice during the development of OIR but found no significant inhibition of retinopathy. However, when IL-18-binding protein was administered during the OIR recovery phase to neutralize endogenous IL-18, OIR was still apparent on Day 24. We therefore concluded that IL-18 regulates pathogenic retinal NV by promoting its regression rather than inhibiting its development. This suggests some useful, new approaches to treating retinopathy in humans.
authors.affiliation: Ophthalmology, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Qiao
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Takeru
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Hijioka
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Jo
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sassa
authors.forename: Chikako
authors.initials: C
authors.lastname: Tsutsumi-Miyahara
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Hata
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010100:Oxygen / Q000494:pharmacology*; D012160:Retina / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D042461:Vascular Endothelial Growth Factor A; C118370:interleukin-18 binding protein; D007371:Interferon-gamma; D010100:Oxygen