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Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract
Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to inves...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683626/ https://www.ncbi.nlm.nih.gov/pubmed/36417410 http://dx.doi.org/10.1371/journal.pone.0273868 |
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author | Nagaya, Masaya Yamaoka, Risa Kanada, Fumito Sawa, Tamotsu Takashima, Masaru Takamura, Yoshihiro Inatani, Masaru Oki, Masaya |
author_facet | Nagaya, Masaya Yamaoka, Risa Kanada, Fumito Sawa, Tamotsu Takashima, Masaru Takamura, Yoshihiro Inatani, Masaru Oki, Masaya |
author_sort | Nagaya, Masaya |
collection | PubMed |
description | Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to investigate the therapeutic effects of histone acetyltransferase (HAT) inhibitors. Among the tested HAT inhibitors, TH1834 was the only one that could reverse most of the opacity once it had formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. In lens cross-sections, vacuoles were present in the tissue of the cortical equatorial region of untreated cataract samples. In treated cataract samples, lens tissue regenerated to fill the vacuoles. To identify the genes regulated by HAT inhibitors, qRT-PCR was performed on treated and untreated cataract samples to determine candidate genes. Expression of Acta1 and Stmn4, both of which are involved in the cytoskeleton, were altered significantly in C646+CPTH2 samples. Expression of Emd, a nuclear membrane protein, and Prtfdc1, which is involved in cancer cell proliferation, were altered significantly in CBP30+CPTH2 samples. Acta1, Acta2, Arrdc3, Hebp2, Hist2h2ab, Pmf1, Ppdpf, Rbm3, RGD1561694, Slc16a6, Slfn13, Tagln, Tgfb1i1, and Tuba1c in TH1834 samples were significantly altered. These genes were primarily related to regulation of cell proliferation, the cytoskeleton, and cell differentiation. Expression levels increased with the onset of cataracts and was suppressed in samples treated with HAT inhibitors. |
format | Online Article Text |
id | pubmed-9683626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-96836262022-11-24 Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract Nagaya, Masaya Yamaoka, Risa Kanada, Fumito Sawa, Tamotsu Takashima, Masaru Takamura, Yoshihiro Inatani, Masaru Oki, Masaya PLoS One Research Article Cataract, a disease that causes opacity of the lens, is the leading cause of blindness worldwide. Cataracts secondary to diabetes are common, even in young patients, so they are of significant clinical importance. Here, we used an ex vivo model of galactose-induced cataracts in the rat lens to investigate the therapeutic effects of histone acetyltransferase (HAT) inhibitors. Among the tested HAT inhibitors, TH1834 was the only one that could reverse most of the opacity once it had formed in the lens. Combination treatment with C646/CPTH2 and CBP30/CPTH2 also had therapeutic effects. In lens cross-sections, vacuoles were present in the tissue of the cortical equatorial region of untreated cataract samples. In treated cataract samples, lens tissue regenerated to fill the vacuoles. To identify the genes regulated by HAT inhibitors, qRT-PCR was performed on treated and untreated cataract samples to determine candidate genes. Expression of Acta1 and Stmn4, both of which are involved in the cytoskeleton, were altered significantly in C646+CPTH2 samples. Expression of Emd, a nuclear membrane protein, and Prtfdc1, which is involved in cancer cell proliferation, were altered significantly in CBP30+CPTH2 samples. Acta1, Acta2, Arrdc3, Hebp2, Hist2h2ab, Pmf1, Ppdpf, Rbm3, RGD1561694, Slc16a6, Slfn13, Tagln, Tgfb1i1, and Tuba1c in TH1834 samples were significantly altered. These genes were primarily related to regulation of cell proliferation, the cytoskeleton, and cell differentiation. Expression levels increased with the onset of cataracts and was suppressed in samples treated with HAT inhibitors. Public Library of Science 2022-11-23 /pmc/articles/PMC9683626/ /pubmed/36417410 http://dx.doi.org/10.1371/journal.pone.0273868 Text en © 2022 Nagaya et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Nagaya, Masaya Yamaoka, Risa Kanada, Fumito Sawa, Tamotsu Takashima, Masaru Takamura, Yoshihiro Inatani, Masaru Oki, Masaya Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract |
title | Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract |
title_full | Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract |
title_fullStr | Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract |
title_full_unstemmed | Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract |
title_short | Histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract |
title_sort | histone acetyltransferase inhibition reverses opacity in rat galactose-induced cataract |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9683626/ https://www.ncbi.nlm.nih.gov/pubmed/36417410 http://dx.doi.org/10.1371/journal.pone.0273868 |
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