Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are o...Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the cell.Nevertheless,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.展开更多
Human cell types affected by retinal diseases(such as age-related macular degeneration or retinitis pimentosa) are limited in cell number and of reduced accessibility. As a consequence, their isolation for in vitro st...Human cell types affected by retinal diseases(such as age-related macular degeneration or retinitis pimentosa) are limited in cell number and of reduced accessibility. As a consequence, their isolation for in vitro studies of disease mechanisms or for drug screening efforts is fastidious. Human pluripotent stem cells(h PSCs), either of embryonic origin or through reprogramming of adult somatic cells,represent a new promising way to generate models of human retinopathies, explore the physiopathological mechanisms and develop novel therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induce pluripotent stem cells together with the continuous improvement of methods to differentiate these cells into disease-affected cellular subtypes opens new perspectives to model and understand a large number of human pathologies, including retinopathies. This review focuses on the added value of h PSCs for the disease modeling of human retinopathies and the study of their molecular pathological mechanisms. We also discuss the recent use of these cells for establishing the validation studies for therapeutic intervention and for the screening of large compound libraries to identify candidate drugs.展开更多
The outer blood-retina barrier(oBRB),crucial for the survival and the proper functioning of the overlying retinal layers,is disrupted in numerous diseases affecting the retina,leading to the loss of the photoreceptors...The outer blood-retina barrier(oBRB),crucial for the survival and the proper functioning of the overlying retinal layers,is disrupted in numerous diseases affecting the retina,leading to the loss of the photoreceptors and ultimately of vision.To study the oBRB and/or its degeneration,many in vitro oBRB models have been developed,notably to investigate potential therapeutic strategies against retinal diseases.Indeed,to this day,most of these pathologies are untreatable,especially once the first signs of degeneration are observed.To cure those patients,a current strategy is to cultivate in vitro a mature oBRB epithelium on a custom membrane that is further implanted to replace the damaged native tissue.After a description of the oBRB and the related diseases,this review presents an overview of the oBRB models,from the simplest to the most complex.Then,we propose a discussion over the used cell types,for their relevance to study or treat the oBRB.Models designed for in vitro applications are then examined,by paying particular attention to the design evolution in the last years,the development of pathological models and the benefits of co-culture models,including both the retinal pigment epithelium and the choroid.Lastly,this review focuses on the models developed for in vivo implantation,with special emphasis on the choice of the material,its processing and its characterization,before discussing the reported pre-clinical and clinical trials.展开更多
基金supported by LifeArc Philanthropic Fund(P2019-0004)LifeArc Pathfinder Award+7 种基金along with Wellcome Trust Seed Award(109626/Z/15/Z)FA PESP-UoB Strategic Collaboration FundBirmingham Fellowship(to SS)grants from Laboratoire d'Excellence Revive(Investissement d'AvenirANR-10-LABX-73)the Region lle-de-France via doctoral school Innovation Therapeutique,du Fondamentalàl'Appliqué(ED569)from Universite Paris-Saclay(to LA)Medical Research Council(MRC)Developmental Pathway Funding Scheme(DPFS)grant(MR/P007732/1)(to TB)supported by the Association Fran?aise contre les Myopathies(AFM-Téléthon)。
文摘Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the cell.Nevertheless,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.
文摘Human cell types affected by retinal diseases(such as age-related macular degeneration or retinitis pimentosa) are limited in cell number and of reduced accessibility. As a consequence, their isolation for in vitro studies of disease mechanisms or for drug screening efforts is fastidious. Human pluripotent stem cells(h PSCs), either of embryonic origin or through reprogramming of adult somatic cells,represent a new promising way to generate models of human retinopathies, explore the physiopathological mechanisms and develop novel therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induce pluripotent stem cells together with the continuous improvement of methods to differentiate these cells into disease-affected cellular subtypes opens new perspectives to model and understand a large number of human pathologies, including retinopathies. This review focuses on the added value of h PSCs for the disease modeling of human retinopathies and the study of their molecular pathological mechanisms. We also discuss the recent use of these cells for establishing the validation studies for therapeutic intervention and for the screening of large compound libraries to identify candidate drugs.
文摘The outer blood-retina barrier(oBRB),crucial for the survival and the proper functioning of the overlying retinal layers,is disrupted in numerous diseases affecting the retina,leading to the loss of the photoreceptors and ultimately of vision.To study the oBRB and/or its degeneration,many in vitro oBRB models have been developed,notably to investigate potential therapeutic strategies against retinal diseases.Indeed,to this day,most of these pathologies are untreatable,especially once the first signs of degeneration are observed.To cure those patients,a current strategy is to cultivate in vitro a mature oBRB epithelium on a custom membrane that is further implanted to replace the damaged native tissue.After a description of the oBRB and the related diseases,this review presents an overview of the oBRB models,from the simplest to the most complex.Then,we propose a discussion over the used cell types,for their relevance to study or treat the oBRB.Models designed for in vitro applications are then examined,by paying particular attention to the design evolution in the last years,the development of pathological models and the benefits of co-culture models,including both the retinal pigment epithelium and the choroid.Lastly,this review focuses on the models developed for in vivo implantation,with special emphasis on the choice of the material,its processing and its characterization,before discussing the reported pre-clinical and clinical trials.
