Attenuation of choroidal neovascularization by histone deacetylase inhibitor.
Choroidal neovascularization (CNV) is a blinding complication of age-related macular degeneration that manifests as the growth of immature choroidal blood vessels through Bruch's membrane, where they can leak fluid or hemorrhage under the retina. Here, we demonstrate that the histone deacetylas...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4373846?pdf=render |
| _version_ | 1818452852421427200 |
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| author | Nymph Chan Shikun He Christine K Spee Keijiro Ishikawa David R Hinton |
| author_facet | Nymph Chan Shikun He Christine K Spee Keijiro Ishikawa David R Hinton |
| author_sort | Nymph Chan |
| collection | DOAJ |
| description | Choroidal neovascularization (CNV) is a blinding complication of age-related macular degeneration that manifests as the growth of immature choroidal blood vessels through Bruch's membrane, where they can leak fluid or hemorrhage under the retina. Here, we demonstrate that the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) can down-regulate the pro-angiogenic hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF), and up-regulate the anti-angiogenic and neuro-protective pigment epithelium derived factor in human retinal pigment epithelial (RPE) cells. Most strikingly, TSA markedly down-regulates the expression of VEGF receptor-2 in human vascular endothelial cells and, thus, can knock down pro-angiogenic cell signaling. Additionally, TSA suppresses CNV-associated wound healing response and RPE epithelial-mesenchymal transdifferentiation. In the laser-induced model of CNV using C57Bl/6 mice, systemic administration of TSA significantly reduces fluorescein leakage and the size of CNV lesions at post-laser days 7 and 14 as well as the immunohistochemical expression of VEGF, VEGFR2, and smooth muscle actin in CNV lesions at post-laser day 7. This report suggests that TSA, and possibly HDACi's in general, should be further evaluated for their therapeutic potential for the treatment of CNV. |
| first_indexed | 2024-12-14T21:29:40Z |
| format | Article |
| id | doaj.art-9d060e9c018343cb8a253698f65b6a80 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T21:29:40Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9d060e9c018343cb8a253698f65b6a802022-12-21T22:46:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012058710.1371/journal.pone.0120587Attenuation of choroidal neovascularization by histone deacetylase inhibitor.Nymph ChanShikun HeChristine K SpeeKeijiro IshikawaDavid R HintonChoroidal neovascularization (CNV) is a blinding complication of age-related macular degeneration that manifests as the growth of immature choroidal blood vessels through Bruch's membrane, where they can leak fluid or hemorrhage under the retina. Here, we demonstrate that the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) can down-regulate the pro-angiogenic hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF), and up-regulate the anti-angiogenic and neuro-protective pigment epithelium derived factor in human retinal pigment epithelial (RPE) cells. Most strikingly, TSA markedly down-regulates the expression of VEGF receptor-2 in human vascular endothelial cells and, thus, can knock down pro-angiogenic cell signaling. Additionally, TSA suppresses CNV-associated wound healing response and RPE epithelial-mesenchymal transdifferentiation. In the laser-induced model of CNV using C57Bl/6 mice, systemic administration of TSA significantly reduces fluorescein leakage and the size of CNV lesions at post-laser days 7 and 14 as well as the immunohistochemical expression of VEGF, VEGFR2, and smooth muscle actin in CNV lesions at post-laser day 7. This report suggests that TSA, and possibly HDACi's in general, should be further evaluated for their therapeutic potential for the treatment of CNV.http://europepmc.org/articles/PMC4373846?pdf=render |
| spellingShingle | Nymph Chan Shikun He Christine K Spee Keijiro Ishikawa David R Hinton Attenuation of choroidal neovascularization by histone deacetylase inhibitor. PLoS ONE |
| title | Attenuation of choroidal neovascularization by histone deacetylase inhibitor. |
| title_full | Attenuation of choroidal neovascularization by histone deacetylase inhibitor. |
| title_fullStr | Attenuation of choroidal neovascularization by histone deacetylase inhibitor. |
| title_full_unstemmed | Attenuation of choroidal neovascularization by histone deacetylase inhibitor. |
| title_short | Attenuation of choroidal neovascularization by histone deacetylase inhibitor. |
| title_sort | attenuation of choroidal neovascularization by histone deacetylase inhibitor |
| url | http://europepmc.org/articles/PMC4373846?pdf=render |
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