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Miho Nozaki, Atsushi Nakajima, Nobutaka Morimoto, Noriaki Kato, Yuichiro Ogura; Anti-Angiogenic Effect of Fidarestat on Laser-Induced Choroidal Neovascularization in Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1788.
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Anti- vascular endothelial growth factor (VEGF) therapy is now standard of care for age-related macular degeneration (AMD), but this treatment requires repetitive vitreous injections for an indefinite period. Recently, it has been reported that the oral anti-cytokine therapy with Fidarestat is useful for prevention of choroidal neovascularization via a suppression of pro-inflammatory cytokine expression. The purpose of this study was to evaluate the anti-angiogenic effect of fidarestat on laser-induced choroidal neovascularization (CNV) model in mice.
CNV was induced by laser injury in C57BL/6J mice, and CNV volumes were measured 7 days later by confocal evaluation of Griffonia simplicifolia Isolectin B4 staining of RPE-choroid flatmounts. The treatment groups were divided as follows: control (Arabic gum oral administration), Fidarestat (4-32mg/kg/day) oral administration (group F), anti-VEGF neutralizing antibody (nAb) (2 or 10 ng) vitreous injection (group V), both Fidarestat (32mg/kg/day) oral administration and anti-VEGF nAb (2 or 10 ng) vitreous injection (group F+V). And gGroup F, group V and group F+V were also divided as follows: start treatment just after laser (group-d0) and start treatment 3 days after laser (group-d3).
Oral administration of Fidarestat suppressed CNV volume in dose-dependent manner. Although group V (2ng)-d0 did not show significant suppression in CNV volume, group F+V (2ng) -d0 showed significant suppression in CNV volume (p<0.001). In group F-d3 and group V-d3, there is no significant suppression in CNV volume, but group F+V-d3 suppressed CNV volume significantly (p<0.05 for VEGF nAb 2ng, p<0.01 for 10ng).
Conclusions: Fidarestat has proven safe in human. Oral administration of Fidarestat showed significant suppression of CNV, and anti-angiogenic effect was reinforced with anti-VEGF nAbs therapy. From our results, oral Fidarestat therapy might reduce the number of vitreous injections in anti-VEGF therapy for AMD.
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