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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327411/ https://www.ncbi.nlm.nih.gov/pubmed/32599451 http://dx.doi.org/10.1016/j.omtn.2020.05.031 |
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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_facet | 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 | Mak, Heather K. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7327411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-73274112020-07-06 MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells 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 Mol Ther Nucleic Acids Article 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. American Society of Gene & Cell Therapy 2020-06-01 /pmc/articles/PMC7327411/ /pubmed/32599451 http://dx.doi.org/10.1016/j.omtn.2020.05.031 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article 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 MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells |
title | MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells |
title_full | MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells |
title_fullStr | MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells |
title_full_unstemmed | MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells |
title_short | MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells |
title_sort | microrna-19a-pten axis is involved in the developmental decline of axon regenerative capacity in retinal ganglion cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327411/ https://www.ncbi.nlm.nih.gov/pubmed/32599451 http://dx.doi.org/10.1016/j.omtn.2020.05.031 |
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