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S. J. Davis, V. V. Lyzogubov, R. G. Tytarenko, A. N. Safar, N. S. Bora, P. S. Bora; The Effect of Nicotine on Anti-VEGF Therapy in a Mouse Model of Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2986.
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To evaluate if nicotine decreases the efficacy of anti-VEGF therapy in the treatment of neovascular age-related macular degeneration (AMD) using a mouse model.
36 mice were divided into 2 groups, one group received nicotine in their water to achieve serum levels found in chronic smokers. The other group was not exposed to nicotine. All had 4 laser spots placed in both eyes inducing choriodal neovascular membranes. Confocal microscopy was used to obtain a baseline volume of the choriodal neovascularization (CNV) at day 7 post laser, then either Bevacizumab or Adioponectin (APN) peptide II was injected intravitreally. APN has been shown previously to be anti-angiogenic and a potent inhibitor of CNV in mice. At 14 and 21 days post laser the volume of the CNV was measured to access response to anti-VEGF treatment.
For the nicotine untreated mice, in the APN treated group, the volume of CNV was 81% and 59% smaller at days 14 and 21 respectively compared to baseline (p<0.05). In the Bevacizumab treated group, the volume of CNV was 90% and 79% smaller at days 14 and 21 respectively compared to baseline (p<0.05).For the nicotine treated mice, at day 14 the volume of CNV was a little smaller but by day 21 there was no statistical difference compared to baseline and the APN group actually had a larger volume than baseline.Comparing nicotine untreated to nicotine treated, the volume of CNV was 58% and 62% smaller in the nicotine untreated group after APN treatment and 73% and 72% smaller after Bevacizumab treatment at days 14 and 21 respectively (p<0.05). There was no statistical difference comparing Bevacizumab to APN in their effect on CNV volume in all groups.
In nicotine untreated mice, both Bevacizumab and APN peptide II significantly reduced the size of the CNV. Comparing nicotine untreated to nicotine treated mice, we showed nicotine significantly blocks the effect of anti-VEGF therapy, both Bevacizumab and APN peptide II, in the treatment of laser induced neovascular age-related macular degeneration.
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