MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells
Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to...
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| Veröffentlicht in: | Molecular therapy. Nucleic acids 2020-09, Vol.21, p.251-263 |
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| creator | Mak, Heather K. Yung, Jasmine S.Y. Weinreb, Robert N. Ng, Shuk Han Cao, Xu Ho, Tracy Y.C. Ng, Tsz Kin Chu, Wai Kit Yung, Wing Ho Choy, Kwong Wai Wang, Chi Chiu Lee, Tin Lap Leung, Christopher Kai-shun |
| description | Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies.
[Display omitted]
This study demonstrates a previously unrecognized involvement of the miR-19a-PTEN axis in axon regenerative capacity of retinal ganglion cells (RGCs) during development. Mak and colleagues show that miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. |
| doi_str_mv | 10.1016/j.omtn.2020.05.031 |
| format | Article |
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[Display omitted]
This study demonstrates a previously unrecognized involvement of the miR-19a-PTEN axis in axon regenerative capacity of retinal ganglion cells (RGCs) during development. Mak and colleagues show that miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors.</description><identifier>ISSN: 2162-2531</identifier><identifier>EISSN: 2162-2531</identifier><identifier>DOI: 10.1016/j.omtn.2020.05.031</identifier><identifier>PMID: 32599451</identifier><language>eng</language><publisher>CAMBRIDGE: Elsevier Inc</publisher><subject>adeno-associated virus ; axon regeneration ; axon regenerative capacity ; Life Sciences & Biomedicine ; Medicine, Research & Experimental ; microRNA-19 ; optic nerve crush ; optic neuropathy ; phosphatase and tensin homolog ; PTEN ; Research & Experimental Medicine ; retinal ganglion cells ; Science & Technology</subject><ispartof>Molecular therapy. Nucleic acids, 2020-09, Vol.21, p.251-263</ispartof><rights>2020 The Authors</rights><rights>Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2020 The Authors 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>25</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000569481200004</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c521t-89463f9be29fe75bcc711b553b5931d7082740652d283117593bc4fd6f7afa3a3</citedby><cites>FETCH-LOGICAL-c521t-89463f9be29fe75bcc711b553b5931d7082740652d283117593bc4fd6f7afa3a3</cites><orcidid>0000-0002-6920-2626 ; 0000-0001-7863-7229</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327411/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327411/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2107,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32599451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mak, Heather K.</creatorcontrib><creatorcontrib>Yung, Jasmine S.Y.</creatorcontrib><creatorcontrib>Weinreb, Robert N.</creatorcontrib><creatorcontrib>Ng, Shuk Han</creatorcontrib><creatorcontrib>Cao, Xu</creatorcontrib><creatorcontrib>Ho, Tracy Y.C.</creatorcontrib><creatorcontrib>Ng, Tsz Kin</creatorcontrib><creatorcontrib>Chu, Wai Kit</creatorcontrib><creatorcontrib>Yung, Wing Ho</creatorcontrib><creatorcontrib>Choy, Kwong Wai</creatorcontrib><creatorcontrib>Wang, Chi Chiu</creatorcontrib><creatorcontrib>Lee, Tin Lap</creatorcontrib><creatorcontrib>Leung, Christopher Kai-shun</creatorcontrib><title>MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells</title><title>Molecular therapy. Nucleic acids</title><addtitle>MOL THER-NUCL ACIDS</addtitle><addtitle>Mol Ther Nucleic Acids</addtitle><description>Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies.
[Display omitted]
This study demonstrates a previously unrecognized involvement of the miR-19a-PTEN axis in axon regenerative capacity of retinal ganglion cells (RGCs) during development. Mak and colleagues show that miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors.</description><subject>adeno-associated virus</subject><subject>axon regeneration</subject><subject>axon regenerative capacity</subject><subject>Life Sciences & Biomedicine</subject><subject>Medicine, Research & Experimental</subject><subject>microRNA-19</subject><subject>optic nerve crush</subject><subject>optic neuropathy</subject><subject>phosphatase and tensin homolog</subject><subject>PTEN</subject><subject>Research & Experimental Medicine</subject><subject>retinal ganglion cells</subject><subject>Science & Technology</subject><issn>2162-2531</issn><issn>2162-2531</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>DOA</sourceid><recordid>eNqNUl1v0zAUjRCITWN_gAeURySU4o_YSSSENIUxKo2BqvFsOc5N5yq1i-1m7N9zS0u1vSAsS7avzzm-vvdk2WtKZpRQ-X418-vkZowwMiNiRjh9lp0yKlnBBKfPH-1PsvMYVwSHJJRJ9jI74Uw0TSnoaXb_1ZrgFzcXBW108f328ia_-GVjPsfpJj9O0OfW5ekO8k8wweg3a3BJj3gyo3WQ-wEJ3uULWIKDoJOdIG_1RhubHnbUBSTrkHCl3XK0iGxhHOOr7MWgxwjnh_Us-_H58rb9Ulx_u5q3F9eFEYymom5KyYemA9YMUInOmIrSTgjeiYbTviI1q0oiBetZzSmtMNqZcujlUOlBc83Psvlet_d6pTbBrnV4UF5b9Sfgw1LpkKwZQRkmS9oNWFDTlKWmGupK6FLWQks2aIlaH_dam223ht5gIYIen4g-vXH2Ti39pCqOWVKKAm8PAsH_3EJMam2jwXJoB34bFStpQxpesQqhbA_F7sQYYDg-Q4naGUBh8mgAtTOAIkKhAZD05nGCR8rfdiPg3R5wD50forHgDBxh6BAhm7KmbGeWEtH1_6Nbm7D33rV-6xJSP-ypgL2dLAR1oPc2gElYfPuvj_wGbk3hfw</recordid><startdate>20200904</startdate><enddate>20200904</enddate><creator>Mak, Heather K.</creator><creator>Yung, Jasmine S.Y.</creator><creator>Weinreb, Robert N.</creator><creator>Ng, Shuk Han</creator><creator>Cao, Xu</creator><creator>Ho, Tracy Y.C.</creator><creator>Ng, Tsz Kin</creator><creator>Chu, Wai Kit</creator><creator>Yung, Wing Ho</creator><creator>Choy, Kwong Wai</creator><creator>Wang, Chi Chiu</creator><creator>Lee, Tin Lap</creator><creator>Leung, Christopher Kai-shun</creator><general>Elsevier Inc</general><general>Elsevier</general><general>American Society of Gene & Cell Therapy</general><scope>6I.</scope><scope>AAFTH</scope><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-6920-2626</orcidid><orcidid>https://orcid.org/0000-0001-7863-7229</orcidid></search><sort><creationdate>20200904</creationdate><title>MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells</title><author>Mak, Heather K. ; Yung, Jasmine S.Y. ; Weinreb, Robert N. ; Ng, Shuk Han ; Cao, Xu ; Ho, Tracy Y.C. ; Ng, Tsz Kin ; Chu, Wai Kit ; Yung, Wing Ho ; Choy, Kwong Wai ; Wang, Chi Chiu ; Lee, Tin Lap ; Leung, Christopher Kai-shun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-89463f9be29fe75bcc711b553b5931d7082740652d283117593bc4fd6f7afa3a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>adeno-associated virus</topic><topic>axon regeneration</topic><topic>axon regenerative capacity</topic><topic>Life Sciences & Biomedicine</topic><topic>Medicine, Research & Experimental</topic><topic>microRNA-19</topic><topic>optic nerve crush</topic><topic>optic neuropathy</topic><topic>phosphatase and tensin homolog</topic><topic>PTEN</topic><topic>Research & Experimental Medicine</topic><topic>retinal ganglion cells</topic><topic>Science & Technology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mak, Heather K.</creatorcontrib><creatorcontrib>Yung, Jasmine S.Y.</creatorcontrib><creatorcontrib>Weinreb, Robert N.</creatorcontrib><creatorcontrib>Ng, Shuk Han</creatorcontrib><creatorcontrib>Cao, Xu</creatorcontrib><creatorcontrib>Ho, Tracy Y.C.</creatorcontrib><creatorcontrib>Ng, Tsz Kin</creatorcontrib><creatorcontrib>Chu, Wai Kit</creatorcontrib><creatorcontrib>Yung, Wing Ho</creatorcontrib><creatorcontrib>Choy, Kwong Wai</creatorcontrib><creatorcontrib>Wang, Chi Chiu</creatorcontrib><creatorcontrib>Lee, Tin Lap</creatorcontrib><creatorcontrib>Leung, Christopher Kai-shun</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Molecular therapy. Nucleic acids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mak, Heather K.</au><au>Yung, Jasmine S.Y.</au><au>Weinreb, Robert N.</au><au>Ng, Shuk Han</au><au>Cao, Xu</au><au>Ho, Tracy Y.C.</au><au>Ng, Tsz Kin</au><au>Chu, Wai Kit</au><au>Yung, Wing Ho</au><au>Choy, Kwong Wai</au><au>Wang, Chi Chiu</au><au>Lee, Tin Lap</au><au>Leung, Christopher Kai-shun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells</atitle><jtitle>Molecular therapy. Nucleic acids</jtitle><stitle>MOL THER-NUCL ACIDS</stitle><addtitle>Mol Ther Nucleic Acids</addtitle><date>2020-09-04</date><risdate>2020</risdate><volume>21</volume><spage>251</spage><epage>263</epage><pages>251-263</pages><issn>2162-2531</issn><eissn>2162-2531</eissn><abstract>Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies.
[Display omitted]
This study demonstrates a previously unrecognized involvement of the miR-19a-PTEN axis in axon regenerative capacity of retinal ganglion cells (RGCs) during development. Mak and colleagues show that miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors.</abstract><cop>CAMBRIDGE</cop><pub>Elsevier Inc</pub><pmid>32599451</pmid><doi>10.1016/j.omtn.2020.05.031</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6920-2626</orcidid><orcidid>https://orcid.org/0000-0001-7863-7229</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | adeno-associated virus axon regeneration axon regenerative capacity Life Sciences & Biomedicine Medicine, Research & Experimental microRNA-19 optic nerve crush optic neuropathy phosphatase and tensin homolog PTEN Research & Experimental Medicine retinal ganglion cells Science & Technology |
| title | MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells |
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