@article{ac418ae5a88e4463bbde5c84362935f3,
title = "Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice",
abstract = "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.",
author = "Takefumi Yamaguchi and Kazunari Higa and Yukari Yagi-Yaguchi and Koji Ueda and Hisashi Noma and Shinsuke Shibata and Toshihiro Nagai and Daisuke Tomida and Ririko Yasu-Mimura and Osama Ibrahim and Ryo Matoba and Kazuo Tsubota and Pedram Hamrah and Jun Yamada and Kohsuke Kanekura and Jun Shimazaki",
note = "Funding Information: We thank J. Hamuro and M. Ueno for providing the iCare equipment to measure IOP in mice and S. Yamagami for teaching us how to collect AqH in mice. We also thank Editage company for English language editing. This study was supported by the Grant-in-Aid for Scientific Research 15K10906 from the Ministry of Education, Culture, Sports, Science and Technology (to T.Y.), Uehara Memorial Foundation (to T.Y.), Oyama Health Foundation (to T.Y.), Takeda Science Foundation (to T.Y.), Japan Research Foundation for Clinical Pharmacology (to T.Y.), research grant from the General Insurance Association of Japan (to T.Y.), and Rohto Research Award (to T.Y.). The funding organizations had no role in the design or conduct of this research. Publisher Copyright: Copyright {\textcopyright} 2020 The Authors",
year = "2020",
month = may,
doi = "10.1126/sciadv.aaz5195",
language = "English",
volume = "6",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "20",
}