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F. C. Schlichtenbrede, T. Euler, F. Rensch, F. vom Hagen, J. B. Jonas; Toxicity Assessment of Intravitreal Triamcinolone and Bevacizumab (Avastin®) in an ex-vivo Mouse Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3385.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreal triamcinolone acetonide (TA) as well as bevacizumab have succesfully been used in various ocular diseases. Here we assess the safety of these recent therapeutic approaches in an ex-vivo mouse model.
Wildtype mice (C57 black) were intravitreally injected with either TA or bevacizumab. Ten and 30 days following treatment, the mice were sacrificed and whole mounted life retinas were analyzed morphologically using 2-Photon microscopy. The retina was counterstained using the polar fluorescent dye sulforhodamine 101 (SR) which labels the extracellular space and thus, allows assessing the tissue structure. Additionally, the retinas were processed for paraffin histology and stained for apoptosis (TUNEL) and tissue activation. Either untreated or sham injected contralateral eyes served as controls.
Retinal morphology was intact following all procedures and time points. Preliminary results suggest that exposure to bevacizumab at 10 days produced mild increase in epiretinal debris as well as minor changes in the ganglion cell layer with widening of intracellular spaces. This phenomenon seemed transient as alterations were less marked at 30 days. No increase in TUNEL-positive cells was observed after exposure to TA or following sham injection. Moderate increase in apoptosis was found following bevacizumab injection at 10 days and to a lesser degree at 30 post injection. No signs of necrosis were found in any group.
For bevacizumab, transient post-injection changes in retinal tissue integrity and apoptotic rate were detected in this ex-vivo model. For intravitreal TA, neither morphological changes nor an increase in apoptosis could be detected in the model. In conclusion, no severe adverse effects were encountered.
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