title: Role of heparin-binding epidermal growth factor-like growth factor in light-induced photoreceptor degeneration in mouse retina.
abstract: OBJECTIVE
  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 β-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.
authors: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors: Yuki
authors: Y
authors: Inoue
authors: Kazuhiro
authors: K
authors: Tsuruma
authors: Tomohiro
authors: T
authors: Nakanishi
authors: Atsushi
authors: A
authors: Oyagi
authors: Yuta
authors: Y
authors: Ohno
authors: Tomohiro
authors: T
authors: Otsuka
authors: Masamitsu
authors: M
authors: Shimazawa
authors: Hideaki
authors: H
authors: Hara
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004596:Electroretinography; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D008027:Light / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology / Q000528:radiation effects; D060888:Real-Time Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins
keywords: age-related macular degeneration; heparin-binding epidermal growth factor–like growth factor (HB-EGF); light-induced retinal degeneration; neuroprotection; photoreceptor