title: Protective Effects of Antiplacental Growth Factor Antibody Against Light-Induced Retinal Damage in Mice.
abstract: OBJECTIVE
  Placental growth factor (PlGF) is part of the VEGF family and is known to be involved in angiogenesis, vasopermeability, and neuroprotection. Recently, PlGF has been reported as a novel therapeutic target for wet AMD. However, there are few reports about the effect of PlGF against dry AMD. Previously, we reported that PlGF has protective effects against retinal neuronal cell damage in vitro. Therefore, we investigated the effects of PlGF against photoreceptor degeneration.
  
  
  METHODS
  In this study, mice were exposed to white light at 8000 lx for 3 hours to induce retinal damage, which was evaluated by recording the electroretinogram amplitude and measuring the outer nuclear layer (ONL) thickness. The mice were injected intravitreally with PlGF before light exposure, PlGF after light exposure, or anti-PlGF antibody before light exposure. RPE-choroid-sclera flat mounts were immunostained with anti-ZO-1 antibody to evaluate the disruption of retinal pigmented epithelium (RPE) cell-cell junctional integrity after light exposure. Furthermore, the expression of VEGF receptor in the retina and RPE-choroid complex after light exposure was measured using Western blot analysis.
  
  
  RESULTS
  Contrary to the expected outcome, PlGF treatment exacerbated the light-induced retinal functional damage and ONL thinning. In contrast, anti-PlGF treatment significantly improved the light-induced retinal degeneration. The disruption of RPE cell-cell junctional integrity after light exposure was suppressed by anti-PlGF treatment. Moreover, the VEGF receptor, which is involved in blood-retinal barrier breakdown, was up-regulated after light exposure.
  
  
  CONCLUSIONS
  These findings suggest that anti-PlGF antibody has protective effects against light-induced retinal degeneration in the murine retina through inhibition of RPE breakdown after light exposure. Thus, anti-PlGF antibody may be useful therapeutic agents in dry AMD.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Izawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Inoue
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ohno
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ojino
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000627:therapeutic use; D015153:Blotting, Western; D004596:Electroretinography; D058449:Intravitreal Injections; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000276:immunology / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000528:radiation effects
chemical_list: D001323:Autoantibodies; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor