Abnormal retinal vascular development in IL-18 knockout mice.
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.
Qiao
Hong
H
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Sonoda
Koh-Hei
KH
Sassa
Yukio
Y
Hisatomi
Toshio
T
Yoshikawa
Hiroshi
H
Ikeda
Yasuhiro
Y
Murata
Toshinori
T
Akira
Shizuo
S
Ishibashi
Tatsuro
T
D042501:Angiogenic Proteins / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D020382:Interleukin-18 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics; D012171:Retinal Vessels / Q000002:abnormalities* / Q000254:growth & development; D015854:Up-Regulation
D042501:Angiogenic Proteins; D017931:DNA Primers; D020382:Interleukin-18