Targeting molecular pathways for the treatment of inherited retinal degeneration  

作　　者：Meltem Kutluer Li Huang Valeria Marigo 

机构地区：[1]Department of Life Sciences, University of Modena and Reggio Emilia

出　　处：《Neural Regeneration Research》2020年第10期1784-1791,共8页中国神经再生研究（英文版）

基　　金：supported by grants from the Telethon Foundation(GGP14180,GGP19113);the European Union(LSHGCT-2005-512036 and transMed,MSCA-ITN-2017-765441)(all to VM)

摘　　要：Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells.Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity with several genes mutated in patients affected by these genetic diseases.The high genetic heterogeneity of these diseases hampers the development of effective therapeutic interventions for the cure of a large cohort of patients.Common cell demise mechanisms can be envisioned as targets to treat patients regardless the specific mutation.One of these targets is the increase of intracellular calcium ions,that has been detected in several murine models of inherited retinal degeneration.Recently,neurotrophic factors that favor the efflux of calcium ions to concentrations below toxic levels have been identified as promising molecules that should be evaluated as new treatments for retinal degeneration.Here,we discuss therapeutic options for inherited retinal degeneration and we will focus on neuroprotective approaches,such as the neuroprotective activity of the Pigment epithelium-derived factor.The characterization of specific targets for neuroprotection opens new perspectives together with many questions that require deep analyses to take advantage of this knowledge and develop new therapeutic approaches.We believe that minimizing cell demise by neuroprotection may represent a promising treatment strategy for retinal degeneration.Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells. Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity with several genes mutated in patients affected by these genetic diseases. The high genetic heterogeneity of these diseases hampers the development of effective therapeutic interventions for the cure of a large cohort of patients. Common cell demise mechanisms can be envisioned as targets to treat patients regardless the specific mutation. One of these targets is the increase of intracellular calcium ions, that has been detected in several murine models of inherited retinal degeneration. Recently, neurotrophic factors that favor the efflux of calcium ions to concentrations below toxic levels have been identified as promising molecules that should be evaluated as new treatments for retinal degeneration. Here, we discuss therapeutic options for inherited retinal degeneration and we will focus on neuroprotective approaches, such as the neuroprotective activity of the Pigment epithelium-derived factor. The characterization of specific targets for neuroprotection opens new perspectives together with many questions that require deep analyses to take advantage of this knowledge and develop new therapeutic approaches. We believe that minimizing cell demise by neuroprotection may represent a promising treatment strategy for retinal degeneration.

关 键 词：ACHROMATOPSIA calcium CALPAINS CALPASTATIN congenital stationary night blindness Leber’s congenital amaurosis retinitis pigmentosa stargardt disease 

分 类 号：R774.13[医药卫生—眼科]