Abstract
P 085
Intravitreal Anti-VEGF therapy in a mouse model of laser induced CNV
Birthe Meyer-Rüsenberg, Anne Wiermann, Sebastian Bigdon, Udo Bartsch, Gisbert Richard, Michelle Berna-Thill, Oliver Zeitz
Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Hamburg-Eppendorf, Hamburg
Objective
Robust animal models for CNV and anti-VEGF therapy are required to gain a more detailed insight into the mechanisms of CNV. Human Anti-VEGF drugs like Bevacizumab (Avastin®) or Ranibizumab (Lucentis®) have become a substantial part of the first-line treatment of wet age-related macular degeneration (AMD). It was shown that Bevacizumab (Avastin®) inhibits (corneal) angiogenesis in a mouse model (Bock F et al., IOVS 2007) although the interaction between Bevacizumab and murine VEGF seems to be very weak (Yu L et al., IOVS 2008). This study was undertaken to evaluate the effect of intravitreal Bevacizumab and 2 murine Anti-VEGF drugs on the dimensions of laser induced choroidal neovascularisation (CNV) in a mouse model.
Methods
42 adult C57BL/6J mice underwent argon laser photocoagulation (140mW, 75μm, 0,2s; 4 spots) in one eye to induce choroidal neovascularisation. Mice were divided into 3 treatment and 1 control group. Immediately after laser coagulation 1 μl of Bevacizumab (25 μg /μl), VEGF Antibody XP-5293 (ProSci Inc.), Anti-Murine VEGF 500-P131 (Peprotech Inc.) (0,5 μg/μl each)) or balanced salt solution (BSS, controls) was injected into the vitreous cavity. 14 days later the mice were sacrificed and their eyes explanted. Choroidal flatmounts were stained with Lectin and visualized by fluorescence microscopy. For statistic calculation, CNVs were averaged for each eye. Results (dimensionless) were analyzed for statistic significance using a student’s t-test.
Results
On average a size of 477.640 was measured in the BSS group compared to 485.725 (Avastin), 572.500 (Prosci) and 379.561 (Peprotech). There was no significant difference shown between the size of the CNVs in therapy and control groups (p>0,05).
Conclusions
The injection of Anti-VEGF drugs did not lead to a significant reduction of the size of the CNVs. Insufficient penetration through the retina or deficient binding or inactivation of VEGF could be conceivable causes. It might also be possible that the role of VEGF in the development of laser induced CNV is overestimated. Further studies are necessary to prove these theses.
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