| First Author | Inoue Y | Year | 2013 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 54 |
| Issue | 6 | Pages | 3815-29 |
| PubMed ID | 23640042 | Mgi Jnum | J:215439 |
| Mgi Id | MGI:5605262 | Doi | 10.1167/iovs.12-11236 |
| Citation | Inoue Y, et al. (2013) Role of heparin-binding epidermal growth factor-like growth factor in light-induced photoreceptor degeneration in mouse retina. Invest Ophthalmol Vis Sci 54(6):3815-29 |
| abstractText | PURPOSE: Although heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been reported to have protective effects against various neuronal cell damage, its role in the retina has not been elucidated. Here, we investigated its role in light-induced photoreceptor degeneration using retinas and ventral forebrain-specific Hb-egf knockout (KO) mice. METHODS: Disruption of Hb-egf was confirmed by beta-galactosidase (LacZ) staining and RT-PCR. Time-dependent changes in retinal HB-EGF were measured using quantitative RT-PCR and Western blotting. Retinal damage was induced by exposure to light. Recombinant human HB-EGF was injected intravitreally. Electroretinogram (ERG) and histological analyses were performed. To evaluate the effect of HB-EGF against light irradiation-induced cell death, 661W cells, a transformed mouse cone cell line, were used. RESULTS: LacZ-positive cells were observed and Hb-egf deletion was confirmed in the retinas of Hb-egf KO mice. Hb-egf and pro-HB-EGF levels were increased after light exposure in wild-type (WT) mice. Exposure to light reduced the a- and b-wave amplitudes of the dark-adapted ERG, and also outer nuclear layer (ONL) thickness, in Hb-egf KO mice versus WT mice. Treatment with HB-EGF improved both the a- and b-wave amplitudes and the thickness of the ONL. The 661W cell death induced by light irradiation was exacerbated by Hb-egf knockdown. HB-EGF also protected against light-induced cell death and reduced reactive oxygen species (ROS) production in 661W cells. HB-EGF treatment improved the a-wave amplitudes and the thickness of the ONL in Hb-egf KO mice. CONCLUSIONS: These data suggest that HB-EGF plays a pivotal role in light-induced photoreceptor degeneration. It therefore warrants investigation as a potential therapeutic target for such light-induced retinal diseases as age-related macular degeneration. |
