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S. Thaler, F. Ziemssen, M. Fiedorowicz, T. Choragiewicz, S. Bolz, E. Zrenner, K.-U. Bartz-Schmidt, F. Schuettauf; In vivo Toxicity Testing of Intravitreal Bevacizumab (Avastin) and Ranibizumab (Lucentis) in Rat Models With and Without Retinal Ganglion Cell Damage. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4579.
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© ARVO (1962-2015); The Authors (2016-present)
To test a potential long term toxicity on RGC and retinal and cellular changes in rats without RGC damage after intravitreal injections of different anti-VEGF antibodies (Bevacizumab and Ranibizumab) and to test a potential modification of retinal ganglion cell (RGC) survival in an in vivo rat model of N-methyl-D-aspartate (NMDA) induced RGC damage.
Bevacizumab (Avastin) at concentrations of 25mg/ml (normal) or 125mg/ml (high) and Ranibizumab (Lucentis) at concentrations of 6mg/ml (normal) or 36mg/ml (high) were injected intravitreally (volume 2µl) in groups of normal rats and rats 1 day after intravitreal NMDA injections (n≥8). Control rats were treated with the respective vehicle. Eyes of all groups were enucleated 1 week after intravitreal injections of Bevacizumab or Ranibizumab at high concentrations. Additionally eyes of normal rats were evaluated 1month or 2 months after normal concentrations. RGC were retrogradely labelled with the fluorescent tracer fluorogold 2 days before enucleation of eyes. RGC counting was performed on retinal wholemounts. Electron microscopy (EM) was performed 2 months after Bevacizumab or Ranibizumab at high concentrations in normal rat eyes.
Bevacizumab and Ranibizumab in normal concentrations did not show a significant reduction of RGC numbers 1 month or 2 months after administration in untreated rats compared to vehicle. NMDA injections reduced RGC numbers by approx. 90%, Bevacizumab or Ranibizumab in normal or high concentrations did not show a significant change in RGC numbers compared to vehicle injected eyes 1 week after NMDA injections. No marked differences in all groups were seen in EM.
Our results show no signficant toxic effect of Bevacizumab and Ranibizumab at all tested concentrations and timeframes on RGC in vivo. Interestingly, Bevacizumab and Ranibizumab injections did not change RGC loss in the NMDA induced damage model. Futher studies have to be undertaken to evaluate if the application of Bevacizumab (Avastin) and Ranibizumab (Lucentis) is save to perform in patients suffering from AMD combined with excitotoxic neuroretinal diseases.
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