Abstract

SO.07.10

VEGF inhibition by Avastin and Lucentis: More than dose-dependent neutralisation?

Klettner A., Roider J.
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Augenheilkunde

Objective: Comparison of the efficiency and mechanisms of VEGF inhibition by Avastin and Lucentis
Methods: Adult retina-RPE-choroid organ cultures prepared from freshly slaughtered porcine eyes were cultivated in a perfusion chamber. On the second day of culture, tissues were treated with Avastin (0,25 mg/ml) or Lucentis (0,125 mg/ml), respectively. The supernatant was collected after various time points and VEGF content was measured by VEGF Elisa (Quantikine Immunoassay, R&D Systems).
Results: Adult retina-RPE-choroid organ cultures constitutively secrete VEGF into the supernatant (200pg/cm² RPE per hour). After treatment with Avastin or Lucentis, VEGF is no longer detectable in the supernatant by Elisa for at least 6 hours.
Conclusions: In the perfusion chamber, media is completely exchanged after 1,5 h of culture. With the media, Lucentis and Avastin is washed out, too. As both substances are still effective after 6 h, a dose-dependent neutralisation of VEGF cannot be the only mechanism of VEGF inhibition. These results indicate that VEGF might have an influence on its own expression by a positive feedback loop. The binding of VEGF to its antibody might impede VEGF secretion by inhibiting such a positive feedback loop. Also, this might be an explanation as to why Avastin and Lucentis show similar beneficial effects.

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