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S. Kaempf, S. Johnen, A. K. Salz, C. Maltusch, R. Lindt, P. Walter, G. Thumann; Retinal Toxicity of Bevacizumab (Avastin) in Organotypic Culture. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5570.
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Repetitive intravitreal injections of bevacizumab (Avastin) are a successful treatment option for exudative age-related macular degeneration (AMD). The aim of this study was to evaluate toxicity of bevacizumab in the adult mammalian neurosensory retina in culture.
Adult porcine neurosensory retina was cultured adjoined to the RPE-choroid layer (Retina-RPE-Choroid complex) in static culture for 3 days whereas neural retina alone was 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 retina alone cultured without bevacizumab were used as controls. After 3 days in culture the neural retina alone and Retina-RPE-Choroid complexes were fixed, embedded in paraffin and sectioned for histological examination and immunohistochemical analysis for the expression of glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, rhodopsin, smooth muscle actin (SMA), and vascular endothelial growth factor (VEGF).
No toxic effects on ganglion cells or photoreceptor cells were observed at any concentration of bevacizumab. The expression of glial proteins was not altered by bevacizumab, which was localized throughout all retinal layers. The only significant change observed was enhanced SMA expression in retina blood vessels cultured in the presence of bevacizumab.
Bevacizumab was well tolerated by ganglion and photoreceptor cells even at concentrations 5-fold 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.
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