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Yuki Inoue, Yuhei Hashimoto, Shinsuke Takata, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideaki Hara; The involvement of heparin-binding epidermal growth factor like growth factor (HB-EGF) on choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):620.
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© ARVO (1962-2015); The Authors (2016-present)
Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been reported to play an essential role in cancer and angiogenesis, its role in the ocular angiogenesis especially choroidal neovascularization (CNV) has not been elucidated. Here, we evaluated the role of HB-EGF in ocular angiogenesis after laser-induced choroidal neovascularization (CNV) using HB-EGF knockout (KO) mice.
We used conditional HB-EGF KO mice lacking in retina and forebrain to examine the role of HB-EGF after laser-induced CNV model. To investigate the expression of HB-EGF and vascular endothelial growth factor (VEGF), we performed Western blot analysis. In an in vitro study, we used human retinal microvascular endothelial cells (HRMECs) to investigate HB-EGF-induced cell proliferation and migration. Moreover, we used CRM-197, an inhibitor of HB-EGF to evaluate the involvement of HB-EGF on cell proliferation and migration in HRMECs.
In HB-EGF KO mice, CNV area was decreased compared with that in WT mice. The reduction rate was about 27%. Moreover, in retinal pigment epithelium (RPE)-choroidal HB-EGF was increased approximately 2.1-hold (versus the control group) at 3 days after laser-induced CNV, and also the expression of VEGF was upregulated from 5 days onwards after laser-induced CNV. HB-EGF or VEGF increased cell proliferation and migration in HRMECs, and combined application of VEGF with HB-EGF enhanced cell proliferation and migration compared with that of VEGF alone. CRM-197 decreased the HB-EGF- and VEGF-induced cell proliferation and migration.
These findings suggest that HB-EGF plays a pivotal role in CNV. It therefore warrants investigation as a potential therapeutic target for such laser-induced CNV as exudative age-related macular degeneration.
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