Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets
Many 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 g...
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| Veröffentlicht in: | Stem cell research & therapy 2016-01, Vol.7 (2), p.2-2, Article 2 |
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| description | Many 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.
In this study, iPSCs were obtained from patients carrying an OPA1 mutation (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.
Mutant OPA1 (+/-) -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.
Our results suggest that apoptosis mediated by OPA1 mutations plays an important role in the pathogenesis of optic atrophy, and both noggin and β-estrogen may represent potential therapeutic agents for OPA1-related optic atrophy. |
| doi_str_mv | 10.1186/s13287-015-0264-1 |
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In this study, iPSCs were obtained from patients carrying an OPA1 mutation (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.
Mutant OPA1 (+/-) -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.
Our results suggest that apoptosis mediated by OPA1 mutations plays an important role in the pathogenesis of optic atrophy, and both noggin and β-estrogen may represent potential therapeutic agents for OPA1-related optic atrophy.</description><identifier>ISSN: 1757-6512</identifier><identifier>EISSN: 1757-6512</identifier><identifier>DOI: 10.1186/s13287-015-0264-1</identifier><identifier>PMID: 26738566</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Carrier Proteins - physiology ; Cell Differentiation ; Cells, Cultured ; Drug Evaluation, Preclinical ; Estradiol - physiology ; GTP Phosphohydrolases - genetics ; Human Embryonic Stem Cells - physiology ; Humans ; Induced Pluripotent Stem Cells - physiology ; Optic atrophy ; Optic Atrophy, Autosomal Dominant - drug therapy ; Optic Atrophy, Autosomal Dominant - genetics ; Optic Atrophy, Autosomal Dominant - pathology ; Pharmaceutical research ; Retinal Ganglion Cells - physiology ; Stem cells</subject><ispartof>Stem cell research & therapy, 2016-01, Vol.7 (2), p.2-2, Article 2</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2016</rights><rights>Chen et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4741-e14e61cc058ab7b6c91044b98bc31f416afe0c002337faa3a7046832624294d33</citedby><cites>FETCH-LOGICAL-c4741-e14e61cc058ab7b6c91044b98bc31f416afe0c002337faa3a7046832624294d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704249/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704249/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26738566$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Jing</creatorcontrib><creatorcontrib>Riazifar, Hamidreza</creatorcontrib><creatorcontrib>Guan, Min-Xin</creatorcontrib><creatorcontrib>Huang, Taosheng</creatorcontrib><title>Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets</title><title>Stem cell research & therapy</title><addtitle>Stem Cell Res Ther</addtitle><description>Many 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.
In this study, iPSCs were obtained from patients carrying an OPA1 mutation (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.
Mutant OPA1 (+/-) -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.
Our results suggest that apoptosis mediated by OPA1 mutations plays an important role in the pathogenesis of optic atrophy, and both noggin and β-estrogen may represent potential therapeutic agents for OPA1-related optic atrophy.</description><subject>Carrier Proteins - physiology</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Drug Evaluation, Preclinical</subject><subject>Estradiol - physiology</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>Human Embryonic Stem Cells - physiology</subject><subject>Humans</subject><subject>Induced Pluripotent Stem Cells - physiology</subject><subject>Optic atrophy</subject><subject>Optic Atrophy, Autosomal Dominant - drug therapy</subject><subject>Optic Atrophy, Autosomal Dominant - genetics</subject><subject>Optic Atrophy, Autosomal Dominant - pathology</subject><subject>Pharmaceutical research</subject><subject>Retinal Ganglion Cells - physiology</subject><subject>Stem cells</subject><issn>1757-6512</issn><issn>1757-6512</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptktuK1TAUhosozjDOA3gjBUH0omNOTdobYRg8DIwIHq5Dmq62Gdqk5iBu8OFN2eO4t5hcJKx860_Wyl8UTzG6wLjhrwOmpBEVwnWFCGcVflCcYlGLiteYPDzYnxTnIdyiPChFiLPHxQnhgjY156fFr4-uh9nYsVQpuuAWNZe9W4xVNpZujUaXKnq3TrsyhQ0ztk8a-nKdkzeri5C5EGEpNcxzKJXtS9PnoBl2G74nTFaNE3i1Qtoko_IjxPCkeDSoOcD53XpWfHv39uvVh-rm0_vrq8ubSjPBcAWYAcdao7pRnei4bjFirGubTlM8MMzVAEgjRCgVg1JUCcR4QwknjLSsp_SseLPXXVO3QK_zi7ya5erNovxOOmXk8Yk1kxzdD8myEmFtFnh5J-Dd9wQhysWErWBlwaUgseCo4U0mM_r8H_TWJW9zeZkSmLScovYvNaoZpLGDy_fqTVReshrTWtQNy9TFf6g8e1iMdhYGk-NHCa-OEjIT4WccVQpBXn_5fMy-OGAnUHOcgpvz_zgbjkG8B7V3IXgY7huHkdysKPdWlNmKcrOixDnn2WHH7zP-GI_-BmAX2Q4</recordid><startdate>20160107</startdate><enddate>20160107</enddate><creator>Chen, Jing</creator><creator>Riazifar, Hamidreza</creator><creator>Guan, Min-Xin</creator><creator>Huang, Taosheng</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160107</creationdate><title>Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets</title><author>Chen, Jing ; Riazifar, Hamidreza ; Guan, Min-Xin ; Huang, Taosheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4741-e14e61cc058ab7b6c91044b98bc31f416afe0c002337faa3a7046832624294d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Carrier Proteins - physiology</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Drug Evaluation, Preclinical</topic><topic>Estradiol - physiology</topic><topic>GTP Phosphohydrolases - genetics</topic><topic>Human Embryonic Stem Cells - physiology</topic><topic>Humans</topic><topic>Induced Pluripotent Stem Cells - physiology</topic><topic>Optic atrophy</topic><topic>Optic Atrophy, Autosomal Dominant - drug therapy</topic><topic>Optic Atrophy, Autosomal Dominant - genetics</topic><topic>Optic Atrophy, Autosomal Dominant - pathology</topic><topic>Pharmaceutical research</topic><topic>Retinal Ganglion Cells - physiology</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Jing</creatorcontrib><creatorcontrib>Riazifar, Hamidreza</creatorcontrib><creatorcontrib>Guan, Min-Xin</creatorcontrib><creatorcontrib>Huang, Taosheng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cell research & therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Jing</au><au>Riazifar, Hamidreza</au><au>Guan, Min-Xin</au><au>Huang, Taosheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets</atitle><jtitle>Stem cell research & therapy</jtitle><addtitle>Stem Cell Res Ther</addtitle><date>2016-01-07</date><risdate>2016</risdate><volume>7</volume><issue>2</issue><spage>2</spage><epage>2</epage><pages>2-2</pages><artnum>2</artnum><issn>1757-6512</issn><eissn>1757-6512</eissn><abstract>Many 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.
In this study, iPSCs were obtained from patients carrying an OPA1 mutation (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.
Mutant OPA1 (+/-) -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.
Our results suggest that apoptosis mediated by OPA1 mutations plays an important role in the pathogenesis of optic atrophy, and both noggin and β-estrogen may represent potential therapeutic agents for OPA1-related optic atrophy.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>26738566</pmid><doi>10.1186/s13287-015-0264-1</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Carrier Proteins - physiology Cell Differentiation Cells, Cultured Drug Evaluation, Preclinical Estradiol - physiology GTP Phosphohydrolases - genetics Human Embryonic Stem Cells - physiology Humans Induced Pluripotent Stem Cells - physiology Optic atrophy Optic Atrophy, Autosomal Dominant - drug therapy Optic Atrophy, Autosomal Dominant - genetics Optic Atrophy, Autosomal Dominant - pathology Pharmaceutical research Retinal Ganglion Cells - physiology Stem cells |
| title | Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets |
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