1. Dual inhibition of VEGF‐A and ANG‐2 reduced the number of TUNEL‐positive cells and improved visual functionality, as revealed by ERG, in a model of sCNV in JR5558 mice
Dual inhibition of VEGF‐A and ANG‐2 reduced the number of TUNEL‐positive cells and improved visual functionality, as revealed by ERG, in a model of sCNV in JR5558 mice ABar graph of TUNEL‐positive cells in the retina of mice treated with 5 mg/kg anti‐VEGF‐A, anti‐ANG‐2, and 3, 5, and 10 mg/kg anti‐VEGF‐A/ANG‐2. Error bars show SEM with n = 6 animals per group and * denotes all significant changes after one‐sided ANOVA (P = 0.0041) and Tukey's multiple t‐test. IgG control is significantly different from anti‐VEGF‐A/ANG‐2 mid (**, P = 0.0077) and high (**, P = 0.0028).B–G(B) IgG control, (C) anti‐VEGF‐A, (D) anti‐ANG‐2, (E–G) anti‐VEGF‐A/ANG‐2 low, mid, and high: representative micrographs of whole‐mount retinae preparations display the reduction in TUNEL‐positive photoreceptor cells (green) clustered around focal neovascular lesions in anti‐VEGF‐A/ANG‐2 (E–G) and, to a lesser extent, anti‐VEGF‐A‐treated (C) and anti‐ANG‐2‐treated (D) groups compared with IgG‐treated controls (B) (scale bar, 200 μm).HERG was used to assess retinal function in response to large‐field flash stimuli under both scotopic and photopic conditions. Representative photopic (light‐adapted) and scotopic (dark‐adapted) flash response series show increased amplitude and reduced latency after treatment with bispecific anti‐VEGF‐A/ANG‐2 compared with IgG control (both 3 mg/kg). ERG shows reduced depression of B‐wave responses in JR5558 mice treated with anti‐VEGF‐A/ANG‐2 compared to IgG control.IMaximum photopic ERG amplitude was increased using anti‐VEGF‐A/ANG‐2 compared to single anti‐VEGF‐A or anti‐ANG‐2 treatments (all at 3 mg/kg). There was a significant increase in amplitude at stimuli > 2 log (cd*s/m2) between the bispecific anti‐VEGF‐A/ANG‐2 and IgG control group under scoptopic and photopic conditions. Asterisk (*) denotes significance after ANOVA and Dunnett's multiple t‐test compared to IgG control compared for each stimuli separately; error bars show SEM with n = 8 animals per group. Under photopic conditions, anti‐VEGF‐A/ANG‐2 reached significance at 2.58 and 2.30 cd*s/m2 with *, P =  and *, P = 0.0479, respectively. Under scotopic conditions, all stimuli reached significance for anti‐VEGF‐A/ANG‐2 at −2.3 cd*s/m2 (*, P = 0.0498); −1.93 cd*s/m2 (**, P = 0.0035); −1.63 and −1.33 cd*s/m2 (****, P < 0.0001); −1.03 cd*s/m2 (***, P = 0.0002); −0.73 cd*s/m2, (**, P = 0.004); −0.43 cd*s/m2, (**, P = 0.0024); −0.13 cd*s/m2 (**, P = 0.0024) and 0.18 cd*s/m2 (**, P = 0.0031). In addition, anti‐ANG‐2 treatment reached significance at −0.13 cd*s/m2 (+P = 0.011) and 0.18 cd*s/m2 (+P = 0.005), respectively.Data information: ERG, electroretinogram; sCNV spontaneous choroidal neovascularization.
Jörg T Regula et al. EMBO Mol Med. 2016;8:
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