FYN regulates aqueous humor outflow and IOP through the phosphorylation of VE-CADHERIN

被引:0
|
作者
Kizhatil, Krishnakumar [1 ]
Clark, Graham M. [2 ]
Sunderland, Daniel K. [2 ]
Bhandari, Aakriti [2 ,3 ]
Horbal, Logan J. [2 ,3 ]
Balasubramanian, Revathi [3 ]
John, Simon W. M. [3 ,4 ]
机构
[1] Ohio State Univ, Med Ctr, Dept Ophthalmol & Visual Sci, Columbus, OH 43210 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
[3] Columbia Univ, Irving Med Ctr, Dept Ophthalmol, New York, NY 10027 USA
[4] Zuckerman Mind Brain Behav Inst, New York, NY 10027 USA
关键词
SCHLEMMS CANAL ENDOTHELIUM; TYROSINE PHOSPHORYLATION; INNER-WALL; INTRAOCULAR-PRESSURE; TRABECULAR MESHWORK; ADHERENS JUNCTIONS; BARRIER FUNCTION; IN-VIVO; SRC; STRESS;
D O I
10.1038/s41467-024-55232-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Schlemm's canal endothelial cells (SECs) serve as the final barrier to aqueous humor (AQH) drainage from the eye. SECs adjust permeability to AQH outflow to modulate intraocular pressure (IOP). The broad identification of IOP-related genes implicates SECs in glaucoma. However, the molecular mechanisms by which SECs sense and respond to pressure changes to regulate fluid permeability and IOP remain largely undefined. We hypothesize that mechano-responsive phosphorylation of the cell adhesion molecule VE-CADHERIN (CDH5) in SECs, by FYN and possibly other SRC family kinases, regulates adherens junction (AJ) permeability to AQH in response to IOP. On experimentally raising IOP in mouse eyes, AJ permeability, CDH5 phosphorylation, and FYN activation at the AJ all increase. FYN null mutant mice display disrupted IOP regulation and reduced AQH outflow. These findings demonstrate an important role of mechanotransducive signaling within SECs in maintaining IOP homeostasis and implicate FYN as a potential target for developing IOP-lowering treatments.
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页数:14
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