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K. Sugitani, M. Nozaki, A. Nakajima, N. Morimoto, N. Kato, Y. Ogura; Oral Anti-Cytokine Therapy for AMD: Fidarestat Suppresses Laser-Induced Choroidal Neovascularization in Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4956.
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Recently, it has been reported that fidarestat suppresses pro-inflammatory cytokine expression. Although intraocular inflammation is not clinically apparent in age-related macular degeneration (AMD), multiple lines of evidence support an influential role for inflammation in this condition.The purpose of this study was to determine whether the oral anti-cytokine therapy with fidarestat could suppress laser-induced choroidal neovascularization (CNV) 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. Fidarestat (32mg/kg/day) was administered orally during 2 days before laser until sacrifice (group F). Anti-vascular endothelial growth factor (VEGF) antibody was injected into the vitreous following laser injury (group V). Group F+V received Fidarestat treatment and anti-VEGF antibody injection. The level of VEGF and monocyte chemotactic protein (MCP)-1 were quantified by ELISA in 3 days after laser injury.
The VEGF and MCP-1 level in the RPE-choroid significantly increased 3 days after laser injury (p<0.05). Fidarestat normalized VEGF expression and reduced MCP-1 expression after laser injury. Fidarestat suppressed CNV volumes compared with control mice. (Control group; 399174±41530µm3, group V; 329265±38720µm3, group F; 174186±13060µm3, group F+V; 141794±11290µm3, p<0.0001). The maximum suppression was detected in group F+V.
Anti-VEGF therapy is now standard care for AMD. Our results may reveal beneficial effects of oral anti-cytokine therapy with fidarestat on laser CNV model, and may be considered further therapeutic potential for AMD with current anti-VEGF therapy.
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