Effects of Bevacizumab (Avastin) on retinal cells in organotypic culture
Stefanie Kaempf 1*,
Sandra Johnen 1,
Anna Katharina Salz 1,
Andreas W.A. Weinberger 1,
Peter Walter 1,
and
Gabriele Thumann 1
1 Department of Ophthalmology and IZKF BIOMAT., RWTH Aachen University, Aachen, Germany
* To whom correspondence should be addressed. E-mail: smueller-kaempf{at}ukaachen.de.
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Abstract |
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ABSTRACT
Purpose: 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.
Methods: Adult porcine neurosensory retinas were cultured adjoined to the RPE 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 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 were slightly increased in Muller cells, whereas glutamine synthetase and rhodopsin were unaffected by bevacizumab. However, we observed significantly enhanced SMA expression in retina blood vessels in retinas cultured in the presence of bevacizumab.
Conclusions: 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.
Key Words:
bevacizumab, neovascularization, retinal vasculature, retinal cell culture, retinal toxicity, VEGF
