PURPOSE: Repetitive intravitreal injections of bevacizumab are a successful treatment option for exudative age-related macular degeneration (AMD). The aim of this study was to evaluate the toxicity of bevacizumab in the adult mammalian neurosensory retina in culture. METHODS: Adult porcine neurosensory retinas were cultured adjoined to the retinal pigment epithelium-choroid layer (retina-RPE-choroid complex) in static culture for 3 days, whereas neural retinas alone were cultured in a perfusion chamber for 3 days. Bevacizumab was added to the culture and perfusion medium at three concentrations (0.25 mg/mL [n = 6], 0.5 mg/mL [n = 6], and 1.25 mg/mL [n = 6]). Retina-RPE-choroid complex and neural retinas alone cultured without bevacizumab were used as controls. After 3 days in culture, the neural retinas alone and the retina-RPE-choroid complexes were analyzed histologically and immunohistochemically for the expression of glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, rhodopsin, smooth muscle actin (SMA), and apoptosis. RESULTS: No toxic effects on ganglion or photoreceptor cells were observed at any concentration of bevacizumab. The expression of GFAP and vimentin was slightly increased in Müller cells, whereas glutamine synthetase and rhodopsin were unaffected by bevacizumab. However, significantly enhanced SMA expression in retina blood vessels was observed in retinas cultured in the presence of bevacizumab. CONCLUSIONS: Bevacizumab was well tolerated by ganglion and photoreceptor cells even at concentrations fivefold higher than those used clinically. The increased expression of SMA is an indication of the loss of functional VEGF modulating smooth muscle cells in mature vessels.
PURPOSE: Repetitive intravitreal injections of bevacizumab are a successful treatment option for exudative age-related macular degeneration (AMD). The aim of this study was to evaluate the toxicity of bevacizumab in the adult mammalian neurosensory retina in culture. METHODS: Adult porcine neurosensory retinas were cultured adjoined to the retinal pigment epithelium-choroid layer (retina-RPE-choroid complex) in static culture for 3 days, whereas neural retinas alone were cultured in a perfusion chamber for 3 days. Bevacizumab was added to the culture and perfusion medium at three concentrations (0.25 mg/mL [n = 6], 0.5 mg/mL [n = 6], and 1.25 mg/mL [n = 6]). Retina-RPE-choroid complex and neural retinas alone cultured without bevacizumab were used as controls. After 3 days in culture, the neural retinas alone and the retina-RPE-choroid complexes were analyzed histologically and immunohistochemically for the expression of glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, rhodopsin, smooth muscle actin (SMA), and apoptosis. RESULTS: No toxic effects on ganglion or photoreceptor cells were observed at any concentration of bevacizumab. The expression of GFAP and vimentin was slightly increased in Müller cells, whereas glutamine synthetase and rhodopsin were unaffected by bevacizumab. However, significantly enhanced SMA expression in retina blood vessels was observed in retinas cultured in the presence of bevacizumab. CONCLUSIONS:Bevacizumab was well tolerated by ganglion and photoreceptor cells even at concentrations fivefold higher than those used clinically. The increased expression of SMA is an indication of the loss of functional VEGF modulating smooth muscle cells in mature vessels.
Authors: Tatiana Flisikowska; Jerome Egli; Angelika Schnieke; Antonio Iglesias; Krzysztof Flisikowski; Marlene Stumbaum; Erich Küng; Martin Ebeling; Roland Schmucki; Guy Georges; Thomas Singer; Mayuko Kurome; Barbara Kessler; Valeri Zakhartchenko; Eckhard Wolf; Felix Weber Journal: Nat Biomed Eng Date: 2022-09-22 Impact factor: 29.234
Authors: Konstantin Astafurov; Cecilia Q Dong; Lampros Panagis; Gautam Kamthan; Lizhen Ren; Anna Rozenboym; Tarique D Perera; Jeremy D Coplan; John Danias Journal: Mol Vis Date: 2014-01-31 Impact factor: 2.367