Overby, Darryl R. and Zhou, Enhua H. and Vargas-Pinto, Rocio and Pedrigi, Ryan M. and Fuchshofer, Rudolf and Braakman, Sietse T. and Gupta, Ritika and Perkumas, Kristin M. and Sherwood, Joseph M. and Vahabikashi, Amir and Quynh Dang, and Kim, Jae Hun and Ethier, C. Ross and Stamer, W. Daniel and Fredberg, Jeffrey J. and Johnson, Mark (2014) Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111 (38). pp. 13876-13881. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
Increased flow resistance is responsible for the elevated intraocular pressure characteristic of glaucoma, but the cause of this resistance increase is not known. We tested the hypothesis that altered biomechanical behavior of Schlemm's canal (SC) cells contributes to this dysfunction. We used atomic force microscopy, optical magnetic twisting cytometry, and a unique cell perfusion apparatus to examine cultured endothelial cells isolated from the inner wall of SC of healthy and glaucomatous human eyes. Here we establish the existence of a reduced tendency for pore formation in the glaucomatous SC cell-likely accounting for increased outflow resistance-that positively correlates with elevated subcortical cell stiffness, along with an enhanced sensitivity to the mechanical microenvironment including altered expression of several key genes, particularly connective tissue growth factor. Rather than being seen as a simple mechanical barrier to filtration, the endothelium of SC is seen instead as a dynamic material whose response to mechanical strain leads to pore formation and thereby modulates the resistance to aqueous humor outflow. In the glaucomatous eye, this process becomes impaired. Together, these observations support the idea of SC cell stiffness-and its biomechanical effects on pore formation-as a therapeutic target in glaucoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INNER-WALL ENDOTHELIUM; AQUEOUS-HUMOR OUTFLOW; TRABECULAR MESHWORK; PORE DENSITY; RESISTANCE; STIFFNESS; EYES; MICROSCOPY; MECHANICS; CULTURE; cell mechanics; primary open-angle glaucoma; modulus; cytoskeleton |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Aug 2019 11:56 |
| Last Modified: | 13 Aug 2019 11:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9531 |
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