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Susan H. Henry, Ewa Budzynski, Christine Diamond, Todd Haight, Olena Iatsenko, Kuo Lee Lieu, Andriy Pashko, Kyoko Mitts, Claes Bavik, Ryo Kubota; Visual Cycle Modulators (VCMs) as Inhibitors of Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):950.
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To test the efficacy of VCMs as inhibitors of retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR) .
Seven-day-old 129S2/SvPasCrl pups were placed in high oxygen (75% O2) for 5 days. On day 12, the animals were then placed in room air and dosed intraperitoneally with ACU-4429 (3mg/kg ), ACU-4935 (0.3mg/kg), positive control (ruboxistaurin, 10mg/kg), or vehicle daily for 5 additional days. Two hours after dosing with VCM or vehicle, the pups were bleached with 10 minutes of 5 klux white light. On P17, the animals were euthanized and the eyes were removed for analysis. Retinas from right eyes were dissected for flat mounts and stained with isolectin B4. The neovascular area was measured for each animal. The left eyes were paraffin-embedded, sectioned, and stained with H&E. The average number of neovascular nuclei was counted for each animal. Differences between treatment groups were analyzed with one-way ANOVA followed by Tukey’s Multiple Comparison Test.
Treatment with either one of the VCMs significantly reduced neovascular area compared to treatment with vehicle. Retinal neovascular area was reduced by 32% with ACU-4429, 23% with ACU-4935, and 29% with ruboxistaurin (positive control); the mean reduction was significantly (p<0.05), greater with either of the VCMs than with vehicle and did not differ significantly (p>0.05) between ruboxistaurin and either of the VCMs.
VCMs seemed to inhibit retinal neovascularization in a mouse model of OIR and are a promising potential treatment for ischemic retina neovascularizations such as diabetic retinopathy.
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