Multikinase-Inhibitoren als therapeutischer Ansatz bei neovaskulärer AMD: In-vitro-Evaluation der Sicherheit von Axitinib, Pazopanib und Sorafenib zur intraokularen Anwendung Multikinase Inhibitors as a New Approach in Neovascular Age-Related Macular Degeneration (AMD) Treatment: In Vitro Safety Evaluations of Axitinib, Pazopanib and Sorafenib for Intraocular Use

Background: Multikinase inhibitors (MKI) inter- fere effectively at different levels of the neovascu- larisation cascade. Early clinical and experimental data suggest that MKIs represent a promising novel approach for the treatment of neovascular age-related macular degeneration (AMD). Howev- er, so far little is known about the biocompatibil- ity of MKIs regarding human ocular cells. This in vitro study investigates and compares the bio- compatibility of three MKIs, axitinib, pazopanib, and sorafenib regarding ocular cells of the anteri- or and posterior segments, as well as organ-cul- tured donor corneas. Methods: Primary human optic nervehead astro- cytes (ONHA), trabecular meshwork cells (TMC), and retinal pigment epithelium (RPE), human corneal endothelial and lens epithelial cells (CEC and LEC) were treated with different concentra- tions of axitinib, pazopanib, or sorafenib (0.1 to 100µg/mL). To simulate oxidative stress, the cells were additionally co-incubated with 400 µM hy- drogen peroxide. Induction of cell death and cel- lular viability were examined by live-dead assay and tetrazolium dye reduction assay (MTT). In ad- dition, the influence of the three substances on human corneal endothelium was evaluated in se- ropositive donor corneas in organ culture by phase contrast microscopy. Results: Up to a concentration of 7.5 mg/mL of the