4.4 Article

Bevacizumab (Avastin) does not harm retinal function after intravitreal injection as shown by electroretinography in adult mice

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LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/IAE.0b013e31815e9368

Keywords

avastin; bevacizumab; BSS; electroretinography; immunohistochemistry; intravitreal injection; mouse; retinal function; toxicity testing

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Purpose: Scavenging of VEGF by specific antibodies is a promising way to treat ocular conditions connected with neovascularization. Intravitreal injections of Avastin (bevacizumab) are performed frequently as a treatment of such conditions. In this study, the authors examine whether the retinal function in wild-type mice is affected by an intravitreal injection of Avastin. Methods: Electroretinography was performed in four different experimental groups of wild-type C57BL/6 mice before treatment and 1, 4, 12, and 25 days afterwards. The first group was injected intravitreally with BSS, the second one received injections of a vehicle solution, and the third group was injected with the commercial Avastin solution. In a fourth group, sham surgery was performed. Immunohistochemistry was performed in some eyes to evaluate penetration of the bevacizumab molecule through the retina. Results: In all four groups, a similar behavior of the ERG parameters could be detected. One day after the injections, the amplitudes showed a clear decrease. Later on, they recovered gradually. No difference could be seen between eyes injected with Avastin or vehicle solution. Bevacizumab immunoreactivity was already present in the whole retina half an hour after the intravitreal injection and was not detectable 25 days later. Moreover, binding of bevacizmab to endogenous mouse VEGF could be shown. Conclusions: Based on the electroretinographic findings, the authors conclude that bevacizumab does not have any toxic effects on the mouse retina and its function. The bevacizumab molecule penetrates the retina quickly. Therefore, it can act safely and very quickly, also in deeper retinal layers after its injection.

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