RGD Reference Report - Interleukin-18 regulates pathological intraocular neovascularization. - Rat Genome Database

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Interleukin-18 regulates pathological intraocular neovascularization.

Authors: Qiao, H  Sonoda, KH  Ikeda, Y  Yoshimura, T  Hijioka, K  Jo, YJ  Sassa, Y  Tsutsumi-Miyahara, C  Hata, Y  Akira, S  Ishibashi, T 
Citation: Qiao H, etal., J Leukoc Biol. 2007 Apr;81(4):1012-21. Epub 2007 Jan 18.
RGD ID: 8655930
Pubmed: PMID:17234681   (View Abstract at PubMed)
DOI: DOI:10.1189/jlb.0506342   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL18HumanRetinal Neovascularization  ISOIl18 (Mus musculus) RGD 
Il18RatRetinal Neovascularization  ISOIl18 (Mus musculus) RGD 
Il18MouseRetinal Neovascularization  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il18  (interleukin 18)

Genes (Mus musculus)
Il18  (interleukin 18)

Genes (Homo sapiens)
IL18  (interleukin 18)


Additional Information