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Shiho Ogami, Shinsaku Yamane, Hiroshi Yamamoto, Yasuo Ochi, Yasushi Hirota; Oral dosing of DHA derivative protects against neovascularization and retinopathy in rat AMD models.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2350.
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© ARVO (1962-2015); The Authors (2016-present)
Docosahexaenoic acid (DHA) is the major fatty acid in the retina, it has been reported that DHA supplements reduce the risk of progression to advanced age-related macular degeneration (AMD). The purpose of this study is to investigate the effect of ONO-A, a novel oral DHA derivative, on neovascularization and retinopathy in rat AMD models.
Anti-angiogenic effect was evaluated using rat laser-induced choroidal neovascularization (CNV) model. After laser treatment to one eye, once daily ONO-A (0.03, 0.1, 0.3, 1 mg/kg) was orally administered for 14 days. Anti-vascular endothelial growth factor (VEGF) reagents were intravitreally administered just after laser treatment. 14 days after laser treatment, CNV area was measured in a choroidal flat mount preparation. The retinoprotective effect was evaluated using a rat light-induced retinal degeneration model. Retinal damage was induced by white fluorescent light (8000 lux) for 3 hours. After light-induced damage to eyes, once daily vehicle or ONO-A (0.03, 0.1, 0.3, 1 mg/kg) was orally administered for 3 days. Pigment epithelium-derived factor (PEDF) was intravitreally administered 2 days before light exposure. The thickness of outer nuclear layer (ONL) was evaluated using immunohistochemistry. DNA arrays were conducted to monitor gene expression in retinal pigment epithelium (RPE) cells following exposure to ONO-A.
In the CNV model, ONO-A significantly reduced the area of laser-induced CNV by 8.5 ± 4.5 % (0.03 mg/kg), 15.2 ± 3.5 % (0.1 mg/kg), 18.1 ± 4.1 % (0.3 mg/kg) and 27.2 ± 5.1 % (1 mg/kg), as well as VEGF reagents such as Pegaptanib (18.0 ± 3.0 %) or Aflibercept (26.1 ± 7.2 %). After light-induction, ONL thicknesses in the vehicle or ONO-A groups were 43.4 ± 0.59 μm or 47.0 ± 1.22 μm (0.03 mg/kg), 48.1 ± 1.00 μm (0.1 mg/kg), 48.7 ± 0.59 μm (0.3 mg/kg), 49.9 ±1.52 μm (1 mg/kg), respectively, suggesting that ONO-A maintained the ONL thickness from retinal damage and the effect was equivalent to PEDF. DNA arrays revealed that several gene-expression such as SNAI2 and MAGEB18 were significantly changed by ONO-A in RPE cells.
In the present study, we have demonstrated that ONO-A has an inhibitory effect on CNV formation and a protective effect on retinal damage. These data indicate that ONO-A has a potential to be an oral drug for wet and dry AMD.
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