Regulation of Trabecular Meshwork Cell Contraction and Intraocular Pressure by miR-200c

AbstractThe trabecular meshwork (TM) constitutes the main pathway for aqueous humor drainage and is exposed to complex intraocular pressure fluctuations. The mechanism of homeostasis in which TM senses changes in intraocular pressure and leads to normal levels of outflow resistance is not yet well understood. Previous reports have shown that Piezo1, a mechanically-activated cation channel, is expressed in TM and isolated TM cells. Therefore, we tested hypothesis that Piezo1 may function in response to membrane tension and stretch in TM. In human trabecular meshwork (hTM) cells, PIEZO1 was showed to be abundantly expressed, and Piezo1 agonist Yoda1 and mechanical stretch caused a Piezo1-dependent Ca2+ influx and release of arachidonic acid and PGE2. Treatment with Yoda1 or PGE2 significantly inhibited hTM cell contraction. These results suggest that mechanical stretch stimuli in TM activates Piezo1 and subsequently regulates TM cell contraction by triggering Ca2+ influx and release of arachidonic acid and PGE2. Thus, Piezo1 could acts as a regulator of intraocular pressure (IOP) within the conventional outflow pathway and could be a novel therapeutic strategy to modulate IOP in glaucoma patients.

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Effects of Endothelin-1 on Human Trabecular Meshwork Cell Contraction

Ophthalmic Research ◽

10.1159/000083021 ◽

2005 ◽

Vol 37 (1) ◽

pp. 43-49 ◽

Cited By ~ 8

Author(s):

Mauro Cellini ◽

Piera Versura ◽

Davide Trerè ◽

Emilio C. Campos

Keyword(s):

Trabecular Meshwork ◽

Cell Contraction ◽

Endothelin 1 ◽

Trabecular Meshwork Cell

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Circumferential trabecular meshwork cell density in the human eye

Experimental Eye Research ◽

10.1016/j.exer.2021.108494 ◽

2021 ◽

Vol 205 ◽

pp. 108494

Author(s):

Markus H. Kuehn ◽

Janice A. Vranka ◽

David Wadkins ◽

Thomas Jackson ◽

Lin Cheng ◽

...

Keyword(s):

Cell Density ◽

Trabecular Meshwork ◽

Human Eye ◽

Trabecular Meshwork Cell

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The pressures in the episcleral veins, Schlemm's canal and the trabecular meshwork in monkeys: Effects of changes in intraocular pressure

Experimental Eye Research ◽

10.1016/s0014-4835(89)80060-0 ◽

1989 ◽

Vol 49 (4) ◽

pp. 645-663 ◽

Cited By ~ 82

Author(s):

Olav Mäepea ◽

Anders Bill

Keyword(s):

Intraocular Pressure ◽

Trabecular Meshwork ◽

Schlemm’S Canal ◽

Schlemm's Canal

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Cyclic Mechanical Stress and Trabecular Meshwork Cell Contractility

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.08-2694 ◽

2009 ◽

Vol 50 (8) ◽

pp. 3826 ◽

Cited By ~ 23

Author(s):

Renata F. Ramos ◽

Grant M. Sumida ◽

W. Daniel Stamer

Keyword(s):

Mechanical Stress ◽

Trabecular Meshwork ◽

Cell Contractility ◽

Trabecular Meshwork Cell

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A Case of Iris Melanocytoma Demonstrating Diffuse Melanocytic Proliferation with Uncontrolled Intraocular Pressure

Case Reports in Ophthalmology ◽

10.1159/000464349 ◽

2017 ◽

Vol 8 (1) ◽

pp. 190-194 ◽

Cited By ~ 2

Author(s):

Mami Kusunose ◽

Yuji Sakino ◽

Yoshihiro Noda ◽

Tsutomu Daa ◽

Toshiaki Kubota

Keyword(s):

Electron Microscopy ◽

Intraocular Pressure ◽

Tumor Cells ◽

Trabecular Meshwork ◽

Light And Electron Microscopy ◽

Secondary Glaucoma ◽

Pigment Dispersion ◽

Large Tumor ◽

History Of ◽

Ring Melanoma

We report a rare case with histologically proven melanocytoma of the iris that demonstrated diffuse melanocytic proliferation with uncontrolled secondary glaucoma and investigate the etiology of the intraocular pressure elevation. The patient was a 78-year-old man with a history of darkened iris of his left eye. The intraocular pressure was 39 mm Hg. A slit-lamp examination showed a diffuse darkened iris, and a gonioscopic examination revealed open angle with circumferential heavy pigmentation. There was no pigment dispersion of the anterior chamber and no pigment deposition of the cornea. We suspected malignant ring melanoma in the left eye and enucleated it. The globe was examined with light and electron microscopy. Light microscopy revealed the presence of heavily pigmented tumor cells in the iris, ciliary body, trabecular meshwork, and Schlemm’s canal. A bleached preparation showed large tumor cells with central and paracentral nuclei without mitosis. Electron microscopy of the trabecular meshwork revealed melanin-bearing tumor cells invading the intertrabecular spaces, and the melanin granules were not phagocytosed in the trabecular cells. The mechanical obstruction of the aqueous flow by the tumor cells may be a major cause of secondary glaucoma in eyes with iris melanocytoma presenting diffuse proliferation.

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Intraocular pressure elevation precedes a phagocytosis decline in a model of pigmentary glaucoma

F1000Research ◽

10.12688/f1000research.13797.1 ◽

2018 ◽

Vol 7 ◽

pp. 174 ◽

Cited By ~ 7

Author(s):

Yalong Dang ◽

Susannah Waxman ◽

Chao Wang ◽

Priyal Shah ◽

Ralitsa T. Loewen ◽

...

Keyword(s):

Intraocular Pressure ◽

Trabecular Meshwork ◽

Ex Vivo ◽

Pigment Dispersion ◽

Pigmentary Glaucoma ◽

Fluorescent Microspheres ◽

Phagocytic Capacity ◽

Pressure Transducers ◽

Intraocular Pressure Elevation ◽

Iop Elevation

Background: Outflow regulation and phagocytosis are key functions of the trabecular meshwork (TM), but it is not clear how the two are related in secondary open angle glaucomas characterized by an increased particle load. We hypothesized that diminished TM phagocytosis is not the primary cause of early ocular hypertension and recreated pigment dispersion in a porcine ex vivo model. Methods: Sixteen porcine anterior chamber cultures received a continuous infusion of pigment granules (Pg), while 16 additional anterior chambers served as controls (C). Pressure transducers recorded the intraocular pressure (IOP). The phagocytic capacity of the trabecular meshwork was determined by fluorescent microspheres. Results: The baseline IOPs in Pg and C were similar (P=0.82). A significant IOP elevation occurred in Pg at 48, 120, and 180 hours (all P<0.01, compared to baseline). The pigment did not cause a reduction in TM phagocytosis at 48 hours, when the earliest IOP elevation occurred, but at 120 hours onward (P=0.001 compared to C). This reduction did not result in an additional IOP increase at 120 or 180 hours compared to the first IOP elevation at 48 hours (P>0.05). Conclusions: In this porcine model of pigmentary glaucoma, an IOP elevation occurs much earlier than when phagocytosis fails, suggesting that two separate mechanisms might be at work.

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Morphological changes in the trabecular meshwork and Schlemm’s canal after treatment with topical intraocular pressure-lowering agents

Scientific Reports ◽

10.1038/s41598-021-97746-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ji-Hye Park ◽

Hyun Woo Chung ◽

Eun Gyu Yoon ◽

Min Jung Ji ◽

Chungkwon Yoo ◽

...

Keyword(s):

Intraocular Pressure ◽

Trabecular Meshwork ◽

Morphological Changes ◽

Open Angle Glaucoma ◽

Anterior Segment ◽

Schlemm’S Canal ◽

Schlemm's Canal ◽

Before And After ◽

Treatment Naïve ◽

Aqueous Outflow

AbstractGlaucoma treatment is usually initiated with topical medication that lowers the intraocular pressure (IOP) by reducing the aqueous production, enhancing the aqueous outflow, or both. However, the effect of topical IOP-lowering medications on the microstructures of the aqueous outflow pathway are relatively unknown. In this retrospective, observational study, 56 treatment-naïve patients with primary open-angle glaucoma were enrolled. Images of the nasal and temporal corneoscleral limbus were obtained using anterior segment optical coherence tomography (AS-OCT). The conjunctival vessels and iris anatomy were used as landmarks to select the same limbal area scan, and the trabecular meshwork (TM) width, TM thickness, and Schlemm’s canal (SC) area were measured before and after using the IOP-lowering agents for 3 months. Among the 56 patients enrolled, 33 patients used prostaglandin (PG) analogues, and 23 patients used dorzolamide/timolol fixed combination (DTFC). After 3 months of DTFC usage, the TM width, TM thickness, and SC area did not show significant changes in either the nasal or temporal sectors. Conversely, after prostaglandin analog usage, the TM thickness significantly increased, and the SC area significantly decreased (all P < 0.01). These findings warrant a deeper investigation into their relationship to aqueous outflow through the conventional and unconventional outflow pathways after treatment with PG analogues.

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SNHG3 cooperates with ELAVL2 to modulate cell apoptosis and extracellular matrix accumulation by stabilizing SNAI2 in human trabecular meshwork cells under oxidative stress

10.21203/rs.3.rs-130712/v1 ◽

2020 ◽

Author(s):

Sizhen Li ◽

Qingsong Yang ◽

Zixiu Zhou ◽

Min Fu ◽

Xiaodong Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Extracellular Matrix ◽

Intraocular Pressure ◽

Oxidative Damage ◽

Trabecular Meshwork ◽

Cell Apoptosis ◽

Cell Injury ◽

Quantitative Polymerase Chain Reaction ◽

Subcellular Fractionation ◽

Cell Counting

Abstract Background: Glaucoma is the main reason for irreversible blindness, and pathological increased intraocular pressure is the leading risk factor for glaucoma. It is reported that trabecular meshwork cell injury is closely associated with the elevated intraocular pressure. The current study aimed to investigate the role of SNHG3 in human trabecular meshwork (HTM) cells under oxidative stress. Methods: A series of experiments including real-time quantitative polymerase chain reaction (RT-qPCR), subcellular fractionation assay, western blot analysis, cell counting kit-8 (CCK-8) assay, RNA pull down, flow cytometry analysis, and RIP assay were employed to explore the biological function and regulatory mechanism of SNHG3 in HTM cells under oxidative stress.Results: First, we observed that H2O2 induced SNHG3 upregulation in HTM cells. Then, we found that SNHG3 silencing alleviated H2O2-induced oxidative damage in HTM cells. Moreover, SNAI2 knockdown alleviated the oxidative damage induced by H2O2 in HTM cells. Mechanistically, SNHG3 bound with ELAVL2 to stabilize SNAI2. Finally, SNAI2 overexpression counteracted the effect of SNHG3 silencing on H2O2-induced HTM cells. Conclusion: Our results demonstrated that SNHG3 cooperated with ELAVL2 to modulate cell apoptosis and extracellular matrix (ECM) accumulation by stabilizing SNAI2 in HTM cells under oxidative stress.

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