Combined therapies to restore vision in Pde6B and Aipl1 murine mutants

Yvan Arsenijevic from the Fondation Asile des Aveugles (Lausanne, Switzerland) is the WPL.

The goal of workpackage 3 is to test the potential synergistic effect of neurotrophic molecules, Ca++-channel blockers and cell-cycle manipulation with gene replacement on photoreceptor survival in Pde6B and Aipl1 deficient models.

Gene replacement may not be efficient enough to restore and maintain vision in models of severe photoreceptor diseases. We propose to combine gene transfer of the wild-type gene with another gene or compound known to partially support photoreceptor survival. Calcium blockers, the neurotrophic factor GDNF and activation of tumour suppressors controlling photoreceptor differentiation will be tested and their biological action compared in Pde6B and Aipl1 mutant mice.
In addition, to determine whether the various factors stimulate similar or divergent pathways, an integrative approach, using micro-array analysis, will be adopted.