Neurotrophin family members as neuroprotectants in retinal degenerations.

Abstract

Inherited retinal degenerations (IRDs) are an untreatable cause of blindness due to photoreceptor apoptosis. Blocking apoptosis by exogenous neurotrophic factor administration is a promising therapeutic strategy in IRDs. The neurotrophin (NT) family are a group of peptide growth factors homologous to nerve growth factor that regulate the development, differentiation, survival, and function of neuronal cells. This mini-review summarizes the preclinical evidence for neuroprotection of photoreceptors by NTs and explores the molecular pathways responsible for this protective effect. Studies published in the literature over the past 20years that report on the effect of NTs on apoptotic photoreceptor death in IRDs and light-induced retinal degeneration, and the cellular pathways involved, are reviewed. Preclinical evidence suggests that exogenous NT administration may be protective against photoreceptor apoptosis. Each NT exerts a neuroprotective effect on photoreceptors that is specific depending upon the model of retinal degeneration and the delivery system. Signaling pathways and retinal cells mediating this effect are still uncertain. Alternatively, different NTs may protect or damage photoreceptors depending on the expression pattern of high- and low-affinity NT receptors on the retinal cells. Although there is evidence that NTs may exert a protective effect, most likely indirectly on photoreceptor cell apoptotic degeneration in IRDs, the precise cellular and molecular mechanisms underlying this effect are still largely unknown. Better understanding of these mechanisms may greatly improve the rationale and efficacy of NT strategy for treatment of IRDs.