Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice

Takefumi Yamaguchi, Kazunari Higa, Yukari Yagi-Yaguchi, Koji Ueda, Hisashi Noma, Shinsuke Shibata, Toshihiro Nagai, Daisuke Tomida, Ririko Yasu-Mimura, Osama Ibrahim, Ryo Matoba, Kazuo Tsubota, Pedram Hamrah, Jun Yamada, Kohsuke Kanekura, Jun Shimazaki

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbereaaz5195
JournalScience Advances
Volume6
Issue number20
DOIs
Publication statusPublished - 2020 May

ASJC Scopus subject areas

  • General

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    Yamaguchi, T., Higa, K., Yagi-Yaguchi, Y., Ueda, K., Noma, H., Shibata, S., Nagai, T., Tomida, D., Yasu-Mimura, R., Ibrahim, O., Matoba, R., Tsubota, K., Hamrah, P., Yamada, J., Kanekura, K., & Shimazaki, J. (2020). Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice. Science Advances, 6(20), [eaaz5195]. https://doi.org/10.1126/sciadv.aaz5195