Abnormal retinal vascular development in IL-18 knockout mice.

Hong Qiao; Koh-Hei Sonoda; Yukio Sassa; Toshio Hisatomi; Hiroshi Yoshikawa; Yasuhiro Ikeda; Toshinori Murata; Shizuo Akira; Tatsuro Ishibashi

doi:10.1038/labinvest.3700115

PubMed · 15122309

Abnormal retinal vascular development in IL-18 knockout mice.

Hong Qiao·Koh-Hei Sonoda·Yukio Sassa·Toshio Hisatomi·Hiroshi Yoshikawa·Yasuhiro Ikeda·Toshinori Murata·Shizuo Akira·Tatsuro Ishibashi

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Abstract

Recent studies have indicated that interleukin 18 (IL-18) might act as either an angiogenic or an angiostatic factor, but the true function of this protein in vascular development is unclear. We therefore investigated the role of IL-18 in the formation of retinal vessels. Development of the retinal vasculature was compared in IL-18 knockout (KO) and wild-type (WT) mice at several different time points. The formation of vessels was evaluated using angiography of flat-mounted retinal samples after inoculation with fluorescein dextran. Retinal samples from both groups were also evaluated through histological examinations, and the expression of angiogenic factors was examined using the reverse-transcription-polymerase chain reaction. The capillary retinal vessels in both WT and IL-18 KO mice had reached the peripheral retina by postnatal day (P) 7. However, IL-18 KO mice showed angiectasis and vascular leakage at P7, especially in the mid-peripheral retina. These symptoms were not observed in WT mice at any stage. Histopathological analysis confirmed abnormal vascular formation in IL-18 KO mice at P14. Interestingly, these abnormalities regressed over time and had disappeared by P84. Several angiogenesis-associated factors, including vascular endothelial growth factor (VEGF), basic fibroblast-growth factor (bFGF), platelet-derived growth factor (PDGF) and pigment epithelium-derived factor (PEDF), were overexpressed in the retinas of IL-18 KO mice compared with those of WT mice at P14. Interferon-gamma was detected only in WT mouse retinas at P14. These results provide new evidence for the role of IL-18 in retinal vascular development.

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Angiogenic Proteins Animals Animals, Newborn Base Sequence DNA Primers Interleukin-18 Mice Mice, Inbred C57BL Mice, Knockout Neovascularization, Pathologic Retinal Vessels Up-Regulation Journal Article Research Support, Non-U.S. Gov't

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Hong Qiao, Koh-Hei Sonoda, Yukio Sassa, Toshio Hisatomi, Hiroshi Yoshikawa, Yasuhiro Ikeda, Toshinori Murata, Shizuo Akira, Tatsuro Ishibashi. 2004. Abnormal retinal vascular development in IL-18 knockout mice.. https://doi.org/10.1038/labinvest.3700115

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