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Interleukin‐18 regulates pathological intraocular neovascularization
Author(s) -
Qiao Hong,
Sonoda KohHei,
Ikeda Yasuhiro,
Yoshimura Takeru,
Hijioka Kuniaki,
Jo YoungJoon,
Sassa Yukio,
TsutsumiMiyahara Chikako,
Hata Yasuaki,
Akira Shizuo,
Ishibashi Tatsuro
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0506342
Subject(s) - biology , pathological , neovascularization , choroidal neovascularization , immunology , angiogenesis , ophthalmology , neuroscience , cancer research , medicine , botany , retinal
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.