The Wnt Signaling Pathway in Retinal Degenerations

The retina is a complex tissue composed of multiple interconnected cell layers, highly specialized for transforming light and color into electrical signals perceived by the brain. Damage or death of the primary light‐sensing cells, the photoreceptors, results in devastating effects on vision. Despite the identification of numerous mutations that cause inherited retinal degenerations, the cellular and molecular mechanisms leading from the primary mutations to photoreceptor apoptosis are not understood. Wnt signaling has essential regulatory functions in a wide variety of critical developmental processes. Our research and others' have suggested that the Wnt pathway may be involved in retinal degeneration. Wnt ligands regulate developmental death of Drosophila photoreceptors, dysregulated Wnt signaling is involved in neuronal degeneration elsewhere in the central nervous system and Wnts control the expression of pro‐survival growth factors in mammalian tissues. Additionally, altered expression of Wnt pathway genes, including the anti‐apoptotic Wnt signaling regulator Dickkopf 3 (Dkk3), were observed during photoreceptor loss. This review examines the evidence and develops a model proposing a pro‐survival role for Wnt signaling during photoreceptor injury. Because manipulating Wnt signaling has been demonstrated to have therapeutic potential for the treatment of Alzheimers disease, understanding the involvement of Wnts in photoreceptor death will determine whether targeting the Wnt pathway should also be considered as a possible therapeutic strategy for retinal degenerations.IUBMB Life, 57: 381‐388, 2005