Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Nagaya, Masaya, Yamaoka, Risa, Kanada, Fumito, Sawa, Tamotsu, Takashima, Masaru, Takamura, Yoshihiro, Inatani, Masaru, Oki, Masaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
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
_version_ 1784835093396717568
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
work_keys_str_mv AT nagayamasaya histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract
AT yamaokarisa histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract
AT kanadafumito histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract
AT sawatamotsu histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract
AT takashimamasaru histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract
AT takamurayoshihiro histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract
AT inatanimasaru histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract
AT okimasaya histoneacetyltransferaseinhibitionreversesopacityinratgalactoseinducedcataract