The role of Wnt signalling in the pathogenesis and therapy of age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is an ever-increasing disease which affects the vision of the elderly in the Western world. No preventive therapy exists so far and slowing its progression is only possible for a fraction of the cases, namely neovascular AMD, in which neovascularisation sprouts from the choriocapillaris layer into the retina. Nevertheless, one potential target for modulation as an AMD therapy is the manipulation of Wnt signalling, and especially its canonical type, the Wnt/β-catenin pathway. Wnt signalling is one of the fundamental cellular pathways involved e.g. in morphogenesis, proliferation, cell polarity, tissue maturation, as well as homeostasis, and apoptosis. The rationale of modulating Wnt signalling in AMD therapy, is that weakened autophagy, autophagy, the means of the cell to remove waste material, as well as increased epithelial-mesenchymal cell type transition (EMT), inflammation, and oxidative stress response have been detected in AMD. Corresponding to these, the upregulation of Wnt signalling pathway has been discovered to be related to this disease. Thus, inhibition of Wnt signalling could be used as in therapy, especially in the more common, dry form of AMD in all its stages. On the other hand, the activation of Wnt signalling could be used in the therapy of advanced neovascular AMD, primarily for maintaining the blood-retinal barrier, which preserves the homeostasis of the retinal vasculature. Therefore, several approaches concerning both the inhibition and upregulation of Wnt signaling are discussed in this review, in the context of potentially developing effective therapies against AMD in the future.