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Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice
Corneal endothelial cell (CEnC) loss after corneal transplantation is the major cause of graft failure and remains a clinically relevant challenge to overcome. Accumulated knowledge derived from long-term clinical outcomes suggested that elevated protein levels in the aqueous humor are associated wi...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220341/ https://www.ncbi.nlm.nih.gov/pubmed/32426498 http://dx.doi.org/10.1126/sciadv.aaz5195 |
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author | Yamaguchi, Takefumi Higa, Kazunari Yagi-Yaguchi, Yukari Ueda, Koji Noma, Hisashi Shibata, Shinsuke Nagai, Toshihiro Tomida, Daisuke Yasu-Mimura, Ririko Ibrahim, Osama Matoba, Ryo Tsubota, Kazuo Hamrah, Pedram Yamada, Jun Kanekura, Kohsuke Shimazaki, Jun |
author_facet | Yamaguchi, Takefumi Higa, Kazunari Yagi-Yaguchi, Yukari Ueda, Koji Noma, Hisashi Shibata, Shinsuke Nagai, Toshihiro Tomida, Daisuke Yasu-Mimura, Ririko Ibrahim, Osama Matoba, Ryo Tsubota, Kazuo Hamrah, Pedram Yamada, Jun Kanekura, Kohsuke Shimazaki, Jun |
author_sort | Yamaguchi, Takefumi |
collection | PubMed |
description | Corneal endothelial cell (CEnC) loss after corneal transplantation is the major cause of graft failure and remains a clinically relevant challenge to overcome. Accumulated knowledge derived from long-term clinical outcomes suggested that elevated protein levels in the aqueous humor are associated with CEnC loss. However, the full spectrum of driver proteins and molecular processes remains to be determined. Here, we defined the somatic microenvironmental landscape and cellular response across human aqueous humor in samples with poor corneal transplantation clinical outcomes using multiomics analyses and clarified specific driver alterations, including complement activation and disturbed energy homeostasis. These driver alterations were also confirmed in aqueous humor from a novel murine model that spontaneously develops iris atrophy, leading to CEnC loss. The application of the integrative multiomics performed in human samples to the novel murine model will help the development of therapeutic modalities for patients with CEnC loss after corneal transplantation. |
format | Online Article Text |
id | pubmed-7220341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-72203412020-05-18 Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice Yamaguchi, Takefumi Higa, Kazunari Yagi-Yaguchi, Yukari Ueda, Koji Noma, Hisashi Shibata, Shinsuke Nagai, Toshihiro Tomida, Daisuke Yasu-Mimura, Ririko Ibrahim, Osama Matoba, Ryo Tsubota, Kazuo Hamrah, Pedram Yamada, Jun Kanekura, Kohsuke Shimazaki, Jun Sci Adv Research Articles Corneal endothelial cell (CEnC) loss after corneal transplantation is the major cause of graft failure and remains a clinically relevant challenge to overcome. Accumulated knowledge derived from long-term clinical outcomes suggested that elevated protein levels in the aqueous humor are associated with CEnC loss. However, the full spectrum of driver proteins and molecular processes remains to be determined. Here, we defined the somatic microenvironmental landscape and cellular response across human aqueous humor in samples with poor corneal transplantation clinical outcomes using multiomics analyses and clarified specific driver alterations, including complement activation and disturbed energy homeostasis. These driver alterations were also confirmed in aqueous humor from a novel murine model that spontaneously develops iris atrophy, leading to CEnC loss. The application of the integrative multiomics performed in human samples to the novel murine model will help the development of therapeutic modalities for patients with CEnC loss after corneal transplantation. American Association for the Advancement of Science 2020-05-13 /pmc/articles/PMC7220341/ /pubmed/32426498 http://dx.doi.org/10.1126/sciadv.aaz5195 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Yamaguchi, Takefumi Higa, Kazunari Yagi-Yaguchi, Yukari Ueda, Koji Noma, Hisashi Shibata, Shinsuke Nagai, Toshihiro Tomida, Daisuke Yasu-Mimura, Ririko Ibrahim, Osama Matoba, Ryo Tsubota, Kazuo Hamrah, Pedram Yamada, Jun Kanekura, Kohsuke Shimazaki, Jun Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice |
title | Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice |
title_full | Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice |
title_fullStr | Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice |
title_full_unstemmed | Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice |
title_short | Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice |
title_sort | pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220341/ https://www.ncbi.nlm.nih.gov/pubmed/32426498 http://dx.doi.org/10.1126/sciadv.aaz5195 |
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