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Ocular neuroprotection by siRNA targeting caspase-2
Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168996/ https://www.ncbi.nlm.nih.gov/pubmed/21677688 http://dx.doi.org/10.1038/cddis.2011.54 |
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author | Ahmed, Z Kalinski, H Berry, M Almasieh, M Ashush, H Slager, N Brafman, A Spivak, I Prasad, N Mett, I Shalom, E Alpert, E Di Polo, A Feinstein, E Logan, A |
author_facet | Ahmed, Z Kalinski, H Berry, M Almasieh, M Ashush, H Slager, N Brafman, A Spivak, I Prasad, N Mett, I Shalom, E Alpert, E Di Polo, A Feinstein, E Logan, A |
author_sort | Ahmed, Z |
collection | PubMed |
description | Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and cleaved (activated) predominantly in RGC. Inhibition of caspase-2 expression by a chemically modified synthetic short interfering ribonucleic acid (siRNA) delivered by intravitreal administration significantly enhanced RGC survival over a period of at least 30 days. This exogenously delivered siRNA could be found in RGC and other types of retinal cells, persisted inside the retina for at least 1 month and mediated sequence-specific RNA interference without inducing an interferon response. Our results indicate that RGC apoptosis induced by optic nerve injury involves activation of caspase-2, and that synthetic siRNAs designed to inhibit expression of caspase-2 represent potential neuroprotective agents for intervention in human diseases involving RGC loss. |
format | Online Article Text |
id | pubmed-3168996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-31689962011-09-20 Ocular neuroprotection by siRNA targeting caspase-2 Ahmed, Z Kalinski, H Berry, M Almasieh, M Ashush, H Slager, N Brafman, A Spivak, I Prasad, N Mett, I Shalom, E Alpert, E Di Polo, A Feinstein, E Logan, A Cell Death Dis Original Article Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and cleaved (activated) predominantly in RGC. Inhibition of caspase-2 expression by a chemically modified synthetic short interfering ribonucleic acid (siRNA) delivered by intravitreal administration significantly enhanced RGC survival over a period of at least 30 days. This exogenously delivered siRNA could be found in RGC and other types of retinal cells, persisted inside the retina for at least 1 month and mediated sequence-specific RNA interference without inducing an interferon response. Our results indicate that RGC apoptosis induced by optic nerve injury involves activation of caspase-2, and that synthetic siRNAs designed to inhibit expression of caspase-2 represent potential neuroprotective agents for intervention in human diseases involving RGC loss. Nature Publishing Group 2011-06 2011-06-16 /pmc/articles/PMC3168996/ /pubmed/21677688 http://dx.doi.org/10.1038/cddis.2011.54 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Ahmed, Z Kalinski, H Berry, M Almasieh, M Ashush, H Slager, N Brafman, A Spivak, I Prasad, N Mett, I Shalom, E Alpert, E Di Polo, A Feinstein, E Logan, A Ocular neuroprotection by siRNA targeting caspase-2 |
title | Ocular neuroprotection by siRNA targeting caspase-2 |
title_full | Ocular neuroprotection by siRNA targeting caspase-2 |
title_fullStr | Ocular neuroprotection by siRNA targeting caspase-2 |
title_full_unstemmed | Ocular neuroprotection by siRNA targeting caspase-2 |
title_short | Ocular neuroprotection by siRNA targeting caspase-2 |
title_sort | ocular neuroprotection by sirna targeting caspase-2 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168996/ https://www.ncbi.nlm.nih.gov/pubmed/21677688 http://dx.doi.org/10.1038/cddis.2011.54 |
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