Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets
Copyright policy )Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets
AbstractBackgroundMany retinal degenerative diseases are caused by the loss of retinal ganglion cells (RGCs). Autosomal dominant optic atrophy is the most common hereditary optic atrophy disease and is characterized by central vision loss and degeneration of RGCs. Currently, there is no effective treatment for this group of diseases. However, stem cell therapy holds great potential for replacing lost RGCs of patients. Compared with embryonic stem cells, induced pluripotent stem cells (iPSCs) can be derived from adult somatic cells, and they are associated with fewer ethical concerns and are less prone to immune rejection. In addition, patient-derived iPSCs may provide us with a cellular model for studying the pathogenesis and potential therapeutic agents for optic atrophy.MethodsIn this study, iPSCs were obtained from patients carrying anOPA1mutation (OPA1+/−-iPSC) that were diagnosed with optic atrophy. These iPSCs were differentiated into putative RGCs, which were subsequently characterized by using RGC-specific expression markers BRN3a and ISLET-1.ResultsMutantOPA1+/−-iPSCs exhibited significantly more apoptosis and were unable to efficiently differentiate into RGCs. However, with the addition of neural induction medium, Noggin, or estrogen,OPA1+/−-iPSC differentiation into RGCs was promoted.ConclusionsOur results suggest that apoptosis mediated byOPA1mutations plays an important role in the pathogenesis of optic atrophy, and both noggin and β-estrogen may represent potential therapeutic agents forOPA1-related optic atrophy.
- University of California System United States
- University of California, Irvine United States
- Cincinnati Children's Hospital Medical Center United States
- University of California, San Francisco United States
- UNIVERSITY OF CALIFORNIA-IRVINE
Retinal Ganglion Cells, 570, Technology, Cells, Human Embryonic Stem Cells, Induced Pluripotent Stem Cells, Drug Evaluation, Preclinical, 610, Regenerative Medicine, Eye, OPA1, Medical and Health Sciences, GTP Phosphohydrolases, Rare Diseases, Noggin, Clinical Research, Stem Cell Research - Nonembryonic - Human, Optic Atrophy, Autosomal Dominant, Humans, Optic atrophy, Eye Disease and Disorders of Vision, Cells, Cultured, Cultured, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Estradiol, Research, Neurosciences, beta-estrogen, Cell Differentiation, Biological Sciences, Stem Cell Research, Preclinical, Optic Atrophy, Induced pluripotent stem cells, Biological sciences, Autosomal Dominant, Neurological, Drug Evaluation, DAPT, Carrier Proteins
Retinal Ganglion Cells, 570, Technology, Cells, Human Embryonic Stem Cells, Induced Pluripotent Stem Cells, Drug Evaluation, Preclinical, 610, Regenerative Medicine, Eye, OPA1, Medical and Health Sciences, GTP Phosphohydrolases, Rare Diseases, Noggin, Clinical Research, Stem Cell Research - Nonembryonic - Human, Optic Atrophy, Autosomal Dominant, Humans, Optic atrophy, Eye Disease and Disorders of Vision, Cells, Cultured, Cultured, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Estradiol, Research, Neurosciences, beta-estrogen, Cell Differentiation, Biological Sciences, Stem Cell Research, Preclinical, Optic Atrophy, Induced pluripotent stem cells, Biological sciences, Autosomal Dominant, Neurological, Drug Evaluation, DAPT, Carrier Proteins
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