Primary Trabecular Meshwork Cells Incubated in Human Aqueous Humor Differ from Cells Incubated in Serum Supplements

AbstractThe inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.

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Restoration of Aqueous Humor Outflow Following Transplantation of iPSC-Derived Trabecular Meshwork Cells in a Transgenic Mouse Model of Glaucoma

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.16-20672 ◽

2017 ◽

Vol 58 (4) ◽

pp. 2054 ◽

Cited By ~ 28

Author(s):

Wei Zhu ◽

Ankur Jain ◽

Oliver W. Gramlich ◽

Budd A. Tucker ◽

Val C. Sheffield ◽

...

Keyword(s):

Mouse Model ◽

Transgenic Mouse ◽

Aqueous Humor ◽

Trabecular Meshwork ◽

Transgenic Mouse Model ◽

Aqueous Humor Outflow ◽

Trabecular Meshwork Cells

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New Insights Into Pathophysiological Mechanisms Regulating Conventional Aqueous Humor Outflow

Medicina ◽

10.3390/medicina49040026 ◽

2013 ◽

Vol 49 (4) ◽

pp. 26 ◽

Cited By ~ 2

Author(s):

Daiva Paulavičiūtė-Baikštienė ◽

Rūta Baršauskaitė ◽

Ingrida Janulevičienė

Keyword(s):

Intraocular Pressure ◽

Aqueous Humor ◽

Trabecular Meshwork ◽

Kinase Inhibitors ◽

Transforming Growth Factor ◽

Protein Kinase Inhibitors ◽

Pathophysiological Mechanisms ◽

Aqueous Humor Outflow ◽

Trabecular Meshwork Cells ◽

Glaucoma Treatment

The aim of the article was to overview the pathophysiology of the conventional outflow pathway, trabecular meshwork, and intraocular pressure and to discuss the options of future glaucoma treatment directed to improvement in aqueous outflow. The literature search in the Medline, Embase, and Cochrane databases from April to May 2012 was performed; a total of 47 articles analyzed. The diminished conventional pathway may be altered by several pathophysiological mechanisms like TM obstruction caused by transforming growth factor-β2, clastic nondeformable cells, macrophages leaking from hypermature cataract, iris pigment, lens capsular fragments after YAG-laser posterior capsulotomy, proteins and their subfragments. It is known that trabecular meshwork contraction reduces outflow, and the actomyosin system is directly linked to this mechanism. New glaucoma drugs are still under investigation, but it is already proven that agents such as latranculin-B are effective in improving aqueous drainage. Selective Rho-associated coiled coilforming protein kinase inhibitors have been shown to cause a significant improvement in outflow facility and may become a new option for glaucoma treatment. Caldesmon negatively regulates actin-myosin interactions and thus increases outflow. Stem cells may replace missing or nonfunctional trabecular meshwork cells and hopefully will bring a new treatment solution. Pathophysiological mechanisms regulating conventional aqueous humor outflow are still not fully understood and require further investigations. Future treatment decisions should be directed to a specific mechanism regulating an elevation in intraocular pressure.

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Effects of Dinucleoside Polyphosphates on Trabecular Meshwork Cells and Aqueous Humor Outflow Facility

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.105.085274 ◽

2005 ◽

Vol 314 (3) ◽

pp. 1042-1051 ◽

Cited By ~ 27

Author(s):

David Soto ◽

Jesús Pintor ◽

Assumpta Peral ◽

Arcadi Gual ◽

Xavier Gasull

Keyword(s):

Aqueous Humor ◽

Trabecular Meshwork ◽

Outflow Facility ◽

Aqueous Humor Outflow ◽

Trabecular Meshwork Cells ◽

Dinucleoside Polyphosphates

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Intracellular Cl regulates Na-K-Cl cotransport activity in human trabecular meshwork cells

AJP Cell Physiology ◽

10.1152/ajpcell.1999.277.3.c373 ◽

1999 ◽

Vol 277 (3) ◽

pp. C373-C383 ◽

Cited By ~ 19

Author(s):

Luanna K. Putney ◽

Cecile Rose T. Vibat ◽

Martha E. O’Donnell

Keyword(s):

Cell Volume ◽

Aqueous Humor ◽

Trabecular Meshwork ◽

Cell Types ◽

Cellular Mechanisms ◽

Outflow Facility ◽

Aqueous Humor Outflow ◽

Trabecular Meshwork Cells ◽

Cotransport System ◽

Stimulation Of

The trabecular meshwork (TM) of the eye plays a central role in modulating intraocular pressure by regulating aqueous humor outflow, although the mechanisms are largely unknown. We and others have shown previously that aqueous humor outflow facility is modulated by conditions that alter TM cell volume. We have also shown that the Na-K-Cl cotransport system is a primary regulator of TM cell volume and that its activity appears to be coordinated with net efflux pathways to maintain steady-state volume. However, the cellular mechanisms that regulate cotransport activity and cell volume in TM cells have yet to be elucidated. The present study was conducted to investigate the hypothesis that intracellular Cl concentration ([Cl]i) acts to regulate TM cell Na-K-Cl cotransport activity, as has been shown previously for some other cell types. We demonstrate here that the human TM cell Na-K-Cl cotransporter is highly sensitive to changes in [Cl]i. Our findings reveal a marked stimulation of Na-K-Cl cotransport activity, assessed as ouabain-insensitive, bumetanide-sensitive K influx, in TM cells following preincubation of cells with Cl-free medium as a means of reducing [Cl]i. In contrast, preincubation of cells with media containing elevated K concentrations as a means of increasing [Cl]i results in inhibition of Na-K-Cl cotransport activity. The effects of reducing [Cl]i, as well as elevating [Cl]i, on Na-K-Cl cotransport activity are concentration dependent. Furthermore, the stimulatory effect of reduced [Cl]i is additive with cell-shrinkage-induced stimulation of the cotransporter. Our studies also show that TM cell Na-K-Cl cotransport activity is altered by a variety of Cl channel modulators, presumably through changes in [Cl]i. These findings support the hypothesis that regulation of Na-K-Cl cotransport activity, and thus cell volume, by [Cl]i may participate in modulating outflow facility across the TM.

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