Modulation of P75NTR/PRONGEF as a therapeutic approach for degenerative retinopathies

Abstract

This chapter describes the experimental validation of neurotrophins / neurotrophin receptors as therapeutic targets for the treatment of retinal neurodegenerative disorders. Neuropathies often have inflammatory or vascular pathologies as part of the disease mechanism (e.g. glaucoma,diabetic retinopathy and retinitis pigmentosa) leading to neuronal death. Maintenance ofneuronal phenotype and neuronal survival are promoted by the neurotrophins / neurotrophinreceptors. These have historically been valued as potentially useful pharmacological targets to foster neuroprotection or neuro-regeneration. This is the concept of "neurotrophin protection". Paradoxically, however, during embryonic development neurotrophins / neurotrophin receptors can promote synaptic pruning and neurodegeneration, and in adult disease states this process is recapitulated to drive neuronal death. This is the concept of "neurotrophin toxicity" and blockingthis process may be beneficial. This chapter compares the traditional therapeutic strategy of "neurotrophin protection" with the emerging "anti-neurotrophin toxicity" therapeutic strategy. Each approach may have a unique value for specific diseases or for specific stages of disease progression, may be combined given that they address different mechanisms of action, or may complement neuro-regenerative strategies.