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Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma

We previously identified and characterized human trabecular meshwork stem cells (TMSCs) based on high expression of ABCG2/p75 positivity and high nucleus to cytoplasmic ratio. These TMSCs expressing high ABCG2 and p75 were located to the insert region of the human TM. Additionally, we demonstrated a...

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Autores principales: Sundaresan, Yogapriya, Manivannan, Lakshmi Priya, Radhakrishnan, Shanthi, Ramasamy, Krishnadas Subbiah, Veerappan, Muthukkaruppan, Chidambaranathan, Gowri Priya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720087/
https://www.ncbi.nlm.nih.gov/pubmed/34972817
http://dx.doi.org/10.1038/s41598-021-03345-1
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author Sundaresan, Yogapriya
Manivannan, Lakshmi Priya
Radhakrishnan, Shanthi
Ramasamy, Krishnadas Subbiah
Veerappan, Muthukkaruppan
Chidambaranathan, Gowri Priya
author_facet Sundaresan, Yogapriya
Manivannan, Lakshmi Priya
Radhakrishnan, Shanthi
Ramasamy, Krishnadas Subbiah
Veerappan, Muthukkaruppan
Chidambaranathan, Gowri Priya
author_sort Sundaresan, Yogapriya
collection PubMed
description We previously identified and characterized human trabecular meshwork stem cells (TMSCs) based on high expression of ABCG2/p75 positivity and high nucleus to cytoplasmic ratio. These TMSCs expressing high ABCG2 and p75 were located to the insert region of the human TM. Additionally, we demonstrated an age-related reduction in the TMSC content which was significantly associated with TM cell loss. In continuation, this study was aimed to determine the TMSC content in glaucomatous donor eyes wherein a drastic reduction in TM cellularity has already been reported. Anterior segments from known glaucomatous (n = 6) and age-matched normal (n = 8) donors were dissected into four quadrants. A minimum of three sections from each quadrant were used for histopathological analysis as well as immunostaining. Analysis of hematoxylin and eosin-stained sections from glaucomatous tissues revealed a decrease in total TM cellularity, thickening of trabecular beams, fusion of trabeculae, absence of patent Schlemm’s canal compared to age-matched controls. In addition, the TM thickness at various positions of the meshwork and the coronal as well as the meridional diameters of the Schlemm’s canal were observed to be significantly reduced in glaucomatous eyes. Further, sections from both the groups were immunostained for universal stem cell marker ABCG2 and neural crest derived stem cell marker p75. The images were acquired using Leica SP8 confocal microscope. Quantification of total TM cellularity based on nuclear counterstain (mean ± SD) using ImageJ identified 69.33 ± 12.77 cells/section in control eyes. In glaucomatous donors, the TM cellularity was found to be reduced significantly to 41.83 ± 9.0 (p = 0.0007). In addition, a reduction in the percentage of TMSCs (cells with high ABCG2 expression and p75 positivity) was evident in glaucomatous donors (0.14 ± 0.17%) compared to age-matched controls (4.73 ± 5.46%) (p = 0.064). Thus, the present study confirmed the significant decline in TM cellularity and a reducing trend in the TMSC content, though this reduction was non-significant in glaucomatous donor eyes. Further studies are essential to elucidate the role of TMSCs in the pathogenesis of primary open angle glaucoma.
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spelling pubmed-87200872022-01-05 Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma Sundaresan, Yogapriya Manivannan, Lakshmi Priya Radhakrishnan, Shanthi Ramasamy, Krishnadas Subbiah Veerappan, Muthukkaruppan Chidambaranathan, Gowri Priya Sci Rep Article We previously identified and characterized human trabecular meshwork stem cells (TMSCs) based on high expression of ABCG2/p75 positivity and high nucleus to cytoplasmic ratio. These TMSCs expressing high ABCG2 and p75 were located to the insert region of the human TM. Additionally, we demonstrated an age-related reduction in the TMSC content which was significantly associated with TM cell loss. In continuation, this study was aimed to determine the TMSC content in glaucomatous donor eyes wherein a drastic reduction in TM cellularity has already been reported. Anterior segments from known glaucomatous (n = 6) and age-matched normal (n = 8) donors were dissected into four quadrants. A minimum of three sections from each quadrant were used for histopathological analysis as well as immunostaining. Analysis of hematoxylin and eosin-stained sections from glaucomatous tissues revealed a decrease in total TM cellularity, thickening of trabecular beams, fusion of trabeculae, absence of patent Schlemm’s canal compared to age-matched controls. In addition, the TM thickness at various positions of the meshwork and the coronal as well as the meridional diameters of the Schlemm’s canal were observed to be significantly reduced in glaucomatous eyes. Further, sections from both the groups were immunostained for universal stem cell marker ABCG2 and neural crest derived stem cell marker p75. The images were acquired using Leica SP8 confocal microscope. Quantification of total TM cellularity based on nuclear counterstain (mean ± SD) using ImageJ identified 69.33 ± 12.77 cells/section in control eyes. In glaucomatous donors, the TM cellularity was found to be reduced significantly to 41.83 ± 9.0 (p = 0.0007). In addition, a reduction in the percentage of TMSCs (cells with high ABCG2 expression and p75 positivity) was evident in glaucomatous donors (0.14 ± 0.17%) compared to age-matched controls (4.73 ± 5.46%) (p = 0.064). Thus, the present study confirmed the significant decline in TM cellularity and a reducing trend in the TMSC content, though this reduction was non-significant in glaucomatous donor eyes. Further studies are essential to elucidate the role of TMSCs in the pathogenesis of primary open angle glaucoma. Nature Publishing Group UK 2021-12-31 /pmc/articles/PMC8720087/ /pubmed/34972817 http://dx.doi.org/10.1038/s41598-021-03345-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Sundaresan, Yogapriya
Manivannan, Lakshmi Priya
Radhakrishnan, Shanthi
Ramasamy, Krishnadas Subbiah
Veerappan, Muthukkaruppan
Chidambaranathan, Gowri Priya
Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma
title Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma
title_full Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma
title_fullStr Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma
title_full_unstemmed Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma
title_short Reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma
title_sort reduction in trabecular meshwork stem cell content in donor eyes with primary open angle glaucoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720087/
https://www.ncbi.nlm.nih.gov/pubmed/34972817
http://dx.doi.org/10.1038/s41598-021-03345-1
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