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Yuki Inoue, Tomohiro Nakanishi, Astushi Oyagi, Yuta Ohno, Tomohiro Otsuka, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideaki Hara; The involvement of heparin-binding epidermal growth factor like growth factor on light-induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5012.
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© ARVO (1962-2015); The Authors (2016-present)
Heparin-binding epidermal growth factor like growth factor (HB-EGF) is a member of the EGF family of growth factor, and has been reported that it protects against various neuronal cell damages and expresses in the retina. Here, we investigated its role in light-induced photoreceptor degeneration using 661W cells, a transformed mouse cone-cell line, and conditional Hb-egf knockout (KO) mice.
661W cells were used to investigate the effect of HB-EGF on light irradiation-induced cell-death using HB-EGF siRNA and HB-EGF treatments. Time-dependent changes in retinal HB-EGF were measured using quantitative RT-PCR and Western blotting. Moreover, disruption of Hb-egf in the retinas from ventral forebrain specific Hb-egf KO mice, was confirmed by LacZ staining and RT-PCR. Retinal damage was induced by exposure to white fluorescentlight. Recombinant human HB-EGF was directly injected into vitreousbody in mice intravitreally. Electroretinogram (ERG) and histological analyses were performed.
The 661W cell death induced by light irradiation was exacerbated by Hb-egf knockdown. Treatment with HB-EGF protected against light-induced cell-death in 661W cells. Hb-egf and pro-HB-EGF levels were increased after light exposure in wild-type (WT) mice. LacZ-positive cells were observed, and Hb-egf deletion was confirmed in the retinas of Hb-egf KO mice. Exposure to white fluorescent light for 3 h reduced the a- and b-wave amplitudes of the dark-adapted ERG, and ONL thickness in Hb-egf KO mice versus WT mice. HB-EGF treatment improved both the a- and b-wave amplitudes, and the thickness of the ONL.
These data suggest that HB-EGF plays a pivotal role in light-induced retinal damage. It may become a potential therapeutic target for age-related macular degeneration.
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