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Abstract

P 086

Intravitreal Wortmannin reduces the size of laser induced CNV in a mouse model

Anne Wiermann, Birthe Meyer-Rüsenberg, Sebastian Bigdon, Udo Bartsch, Gisbert Richard, Michelle Thill, Oliver Zeitz
Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Hamburg-Eppendorf, Hamburg

Objective
Vascular endothelial growth factor (VEGF) plays a role in exsudative age-related macular degeneration. It mediates migration and proliferation of endothelial cells by phosphorylation of Akt. Wortmannin, an inhibitor of the phosphatidylinositol 3-kinase, specifically blocks Akt phosphorylation. The gain of this study was the evaluation of the effect of intravitreally injected wortmannin on the development of laser induced choroidal neovascularisation (CNV) in a mouse model.
Methods
Twenty-four adult mice (C57BL/6J) underwent argon laser coagulation treatment of the retina around the optic nerve head (4 spots, 75 µm, 140 mW, 50 ms) in one eye to induce choroidal neovascularisation. One hour after laser treatment fifteen mice received 1 microlitre of balanced salt solution (BSS) intravitreal and nine mice received 1 microlitre of wortmannin (0.5 mg/ml). After 14 days the mice were sacrificed and their eyes were explanted. The CNVs were labelled, visualized by fluorescence microscopy and measured using a calculating software (Image Tool). For statistical analyses an unpaired t-test was used.
Results
The intravitreal injection of wortmannin reduced the size of the CNVs from 477640 ±149316 pixels (BSS group) to 269229 ± 69764 pixels (p < 0,0005).
Conclusions
Wortmannin inhibits the development of laser induced CNV in mice. Therefore, PI3-kinase inhibitors might be an interesting new concept of the treatment of patients suffering from exsudative age-related macular degeneration.

 
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