Regulation of intraocular pressure by microRNA cluster miR-143/145

Author(s): Li X (1,2), Zhao F (3,4), Xin M (5), Li G (6), Luna C (6), Li G (1), Zhou Q (4), He Y (2), Yu B (4), Olson E (7), Gonzalez P (6), Wang S (8,9)

1 Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Wuhan, Hubei, 430030, P.R. China.
2 Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
3 Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang City, Liaoning Province, China.
4Department of Cell and Molecular Biology, Tulane University, 2000 Percival Stern Hall, 6400 Freret Street, New Orleans, LA, 70118, USA.
5 Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, 45247, OH, USA.
6 Department of Ophthalmology, Duke University, Durham, North Carolina, USA.
7 Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
8 Department of Cell and Molecular Biology, Tulane University, 2000 Percival Stern Hall, 6400 Freret Street, New Orleans, LA, 70118, USA. swang1@tulane.edu.
9 Department of Ophthalmology, Tulane University School of Medicine, 1430 Tulane Avenue, SL-69, New Orleans, LA, 70112, USA. swang1@tulane.edu.

Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye.

Targeted deletion of miR-143/145 in mice results in significantly reduced IOP, consistent with an ~2-fold increase in outflow facilities. However, aqueous humor production in the same mice appears to be normal based on a microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145 regulates actin dynamics and the contractility of TM cells, consistent with its regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well as myosin light chain kinase (MLCK) in these cells. Our data establish miR-143/145 as important regulators of IOP, which may have important therapeutic implications in glaucoma.

PMID: 28424493

http://www.ncbi.nlm.nih.gov/pubmed/28424493

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