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Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of β-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.
This article was published in the following journal.
Name: Journal of cellular and molecular medicine
Glaucoma is a leading cause of irreversible blindness worldwide. Current treatments of glaucoma involve lowering the IOP by means of decreasing aqueous humor production or increasing non-trabecular aq...
Glaucoma, one of the leading causes of blindness, is an eye disease caused by irregularities in the ocular aqueous outflow system causing an elevated intraocular pressure. High resolution imaging of t...
Trabecular meshwork (TM) cells detect and coordinate responses to intraocular pressure (IOP) in the eye. TM cells become dysfunctional in glaucoma where IOP is often elevated. Recently, we showed that...
Transforming growth factor-β2 (TGFβ2) and Toll-like receptor 4 (TLR4) crosstalk have been implicated in extracellular matrix regulation in the trabecular meshwork (TM) and ocular hypertension in mic...
Glaucoma has been the leading cause of irreversible blindness worldwide. High intraocular pressure (IOP) is a high-risk factor of glaucoma, repression of which has been the important treatment of glau...
This study was to assess the distinct expression of matrix metalloproteinase 13,tissue inhibitor of metalloproteinases 3, and calcium-sensing receptor, in human trabecular meshwork between...
The purpose of this study is to try to identify the cause of damage to the drainage system of the eye (the trabecular meshwork). Damage to this system may cause elevation in the pressure w...
The Kahook Dual Blade is a single-use device specially designed to create a clean cut in the trabecular meshwork. This ablation in the trabecular meshwork allows a better outflow of the aq...
Laser Trabeculoplasty has been shown to be effective in lowering intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG). Although initially demonstrated with the A...
The purpose of this study is to learn how pigment is released from the iris (the colored part of the eye) in patients with pigment dispersion syndrome. It will do this by examining the re...
A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the canal of Schlemm.
Any surgical procedure for treatment of glaucoma by means of puncture or reshaping of the trabecular meshwork. It includes goniotomy, trabeculectomy, and laser perforation.
Glaucoma in which the angle of the anterior chamber is open and the trabecular meshwork does not encroach on the base of the iris.
Neoplasms composed of fatty tissue or connective tissue made up of fat cells in a meshwork of areolar tissue. The concept does not refer to neoplasms located in adipose tissue.
The deposition of flaky, translucent fibrillar material most conspicuous on the anterior lens capsule and pupillary margin but also in both surfaces of the iris, the zonules, trabecular meshwork, ciliary body, corneal endothelium, and orbital blood vessels. It sometimes forms a membrane on the anterior iris surface. Exfoliation refers to the shedding of pigment by the iris. (Newell, Ophthalmology, 7th ed, p380)
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...