Abstract

SA.08.08

Toxicity assessment of intravitreal Triamcinolone and Bevacizumab (Avastin^®) in an ex-vivo mouse model using 2 photon microscopy

Schlichtenbrede F. C.¹, Euler T.², Mittmann W.², Rensch F.¹, Jonas J. B.^1
1Universitäts Augenklinik, Mannheim, Universität Heidelberg; ²Max-Planck-Institut für Medizinische Forschung, Heidelberg

Objective: Intravitreal triamcinolone acetonide (TA) as well as Bevacizumab (Avastin^®, Av) have succesfully been used in various ocular diseases. Here we assess the safety of this recent therapeutic approaches in an ex-vivo mouse model.
Methods: Wildtype mice (C57 black) were intravitreally injected with either TA or Av. 10 and 30 days following treatment mice were sacrificed and whole mounted life retinas were analysed morphologically using 2-Photon microscopy. Additionally the retinas were processed for paraffin histology and stained for Apoptosis (Tunel) and tissue activation (GFAP). Either untreated or sham injected contralateral eyes served as controls.
Results: Retinal morphology was intact following all procedures and time points. Exposure to Av at 10 days produced mild increase in epiretinal debris as well as some changes in the ganglion cell layer with widening of intracellular spaces. This phenomenon seemed transient as alteration 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 Av injection at 10 days and to a lesser degree at 30 post injection. No signs of necrosis were found in any group.
Conclusions: With TA no morphologic changes or an increase in apoptosis could be detected in this ex vivo model. For Av transient post-operative changes in tissue integrity and apopototic rate were apprechiable in our model. In conclusion no severe advese effects which would compromise safety could be observed.

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