Abstract

Glaucoma is the leading cause of irreversible vision loss, and reducing elevated intraocular pressure is currently the only effective clinical treatment. The trabecular meshwork is the main resistance site for aqueous outflow that maintains intraocular pressure. In this study, we transplanted human trabecular meshwork stem cells (TMSCs) intracamerally into mice that received laser photocoagulation over a 180° arc of the trabecular meshwork. TMSCs preferentially homed and integrated to the laser-damaged trabecular meshwork region and expressed differentiated cell markers at 2 and 4 weeks. Laser-induced inflammatory and fibrotic responses were prevented by TMSC transplantation with simultaneous ultrastructure and function restoration. Cell affinity and migration assays and elevated expression of CXCR4 and SDF1 in laser-treated mouse trabecular meshwork suggest that the CXCR4/SDF1 chemokine axis plays an important role in TMSC homing. Our results suggest that TMSCs may be a viable candidate for trabecular meshwork refunctionalization as a novel treatment for glaucoma.

Hongmin Yun et al. show that implanted human stem cells can accurately home to and repair damaged trabecular meshwork tissue in the mouse eye via a chemokine axis defined by CXCR4 and SDF1. The study suggests that stem cells from the trabecular meshwork could be used to refunctionalize the outflow pathway as a treatment for glaucoma.

Details

Title
Human stem cells home to and repair laser-damaged trabecular meshwork in a mouse model
Author
Yun Hongmin 1 ; Wang, Yiwen 2 ; Zhou, Yi 2 ; Wang, Ke 3 ; Sun, Ming 4 ; Stolz, Donna B 5 ; Xia Xiaobo 6 ; Ross, Ethier C 3 ; Du Yiqin 7   VIAFID ORCID Logo 

1  University of Pittsburgh, Department of Ophthalmology, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
2  University of Pittsburgh, Department of Ophthalmology, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000); Central South University, Department of Ophthalmology, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
3  Georgia Institute of Technology/Emory University, Department of Biomedical Engineering, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
4  University of Pittsburgh, Department of Cell Biology, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
5  University of Pittsburgh, Department of Cell Biology, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000); University of Pittsburgh, McGowan Institute for Regenerative Medicine, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
6  Central South University, Department of Ophthalmology, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164) 
7  University of Pittsburgh, Department of Ophthalmology, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000); University of Pittsburgh, McGowan Institute for Regenerative Medicine, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000); University of Pittsburgh, Department of Developmental Biology, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
Publication year
2018
Publication date
2018
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-018-0227-z
ProQuest document ID
2389697685
Copyright
© The Author(s) 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.