Mechanotransduction Channels of the Trabecular Meshwork

Tran, Vu; Ho, Phi; Cabrera, Lais; Torres, Juan; Bhattacharya, Sanjoy K.

doi:10.3109/02713683.2013.842593

Cited by 29 publications

(18 citation statements)

References 55 publications

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“…Mechanosensing and mechanotransducing molecules are present in the TM, despite being a very low fluid flow tissue (Goel et al, 2010; Goel et al, 2011; Goel et al, 2012; Tran et al, 2014). The TM mechanosensing axis involves two parts - mechanosensing in the solution phase in the extracellular matrix (ECM) such as with cochlin (Goel et al, 2012) and mechanotransduction on the TM cell surface by various channels (Tran et al, 2014). …”

Section: Mechanosensory Structural Components Of the Ah Outflow Symentioning

confidence: 99%

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Carreon

Merwe

Fellman

et al. 2017

Progress in Retinal and Eye Research

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In glaucoma, lowered intraocular pressure (IOP) confers neuroprotection. Elevated IOP characterizes glaucoma and arises from impaired aqueous humor (AH) outflow. Increased resistance in the trabecular meshwork (TM), a filter-like structure essential to regulate AH outflow, may result in the impaired outflow. Flow through the 360° circumference of TM structures may be non-uniform, divided into high and low flow regions, termed as segmental. After flowing through the TM, AH enters Schlemm’s canal (SC), which expresses both blood and lymphatic markers; AH then passes into collector channel entrances (CCE) along the SC external well. From the CCE, AH enters a deep scleral plexus (DSP) of vessels that typically run parallel to SC. From the DSP, intrascleral collector vessels run radially to the scleral surface to connect with AH containing vessels called aqueous veins to discharge AH to blood-containing episcleral veins. However, the molecular mechanisms that maintain homeostatic properties of endothelial cells along the pathways are not well understood. How these molecular events change during aging and in glaucoma pathology remain unresolved. In this review, we propose mechanistic possibilities to explain the continuum of AH outflow control, which originates at the TM and extends through collector channels to the episcleral veins.

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Section: Mechanosensory Structural Components Of the Ah Outflow Symentioning

confidence: 99%

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Carreon

Merwe

Fellman

et al. 2017

Progress in Retinal and Eye Research

Self Cite

240

196

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“…Despite its importance, identification of the mechanosensor/s has not been however a subject of extensive number of reports in the literature. Trabecular meshwork cells have been shown to express several known mechanotransduction channels (Piezo1, Piezo2, TASK1, TREK1, TRPA1, TRPC1, TRPC2, TRPC3, TRPC6, TRPM2, TRPP2) in tissue as well as in cultured conditions (Grierson and Lee, 1975b; 1975a; Johnstone and Grant, 1973; Li et al, 2007; Tran et al, 2014). Which, if any, does indeed function as mechanosensor in TM cells is currently unknown.…”

Section: Mechanical Forces In the Outflow Pathway: Critical Regulamentioning

confidence: 99%

Autophagy and mechanotransduction in outflow pathway cells

Hirt

Liton

2017

Experimental Eye Research

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Because of elevations in IOP and other forces, cells in the trabecular meshwork (TM) are constantly subjected to mechanical strain. In order to preserve cellular function and regain homeostasis, cells must sense and adapt to these morphological changes. We and others have already shown that mechanical stress can trigger a broad range of responses in TM cells; however, very little is known about the strategies that TM cells use to respond to this stress, so they can adapt and survive. Autophagy, a lysosomal degradation pathway, has emerged as an important cellular homeostatic mechanism promoting cell survival and adaptation to a number of cytotoxic stresses. Our laboratory has reported the activation of autophagy in TM cells in response to static biaxial strain and high pressure. Moreover, our newest data also suggest the activation of chaperon-assisted selective autophagy, a recently identified tension-induced autophagy essential for mechanotransduction, in TM cells under cyclic mechanical stress. In this review manuscript we will discuss autophagy as part of an integrated response triggered in TM cells in response to strain, exerting a dual role in repair and mechanotransduction, and the potential effects of dysregulated in outflow pathway pathophysiology.

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“…The proteolytic degradation of ECM components probably affects structural organization and alters biological interactions, leading to modified outflow resistance (Keller et al, ). Increased IOP induces a multitude of changes—resulting in cytoskeleton reorganization and alterations of cell shape and motility—involving high‐conductance Ca2 + ‐activated K + channels (Gasull et al, ) and other mechanotransduction channels (Tran et al, ), though the real significance of these changes is not yet understood. It is interesting that early damage to the retinal nerve fiber layer (RNFL), whose alteration is an early indicator of glaucomatous damage, occurs in its cytoskeleton: irregular staining of F‐actin, microtubules and neurofilaments has been found within bundles (Huang et al, ).…”

Section: The Trabecular Meshworkmentioning

confidence: 99%

The Outflow Pathway: A Tissue With Morphological and Functional Unity

Saccà

Gandolfi

Bagnis

et al. 2016

Journal Cellular Physiology

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The trabecular meshwork (TM) plays an important role in high-tension glaucomas. Indeed, the TM is a true organ, through which the aqueous humor flows from the anterior chamber to Schlemm's canal (SC). Until recently, the TM, which is constituted by endothelial-like cells, was described as a kind of passive filter. In reality, it is much more. The cells delineating the structures of the collagen framework of the TM are endowed with a cytoskeleton, and are thus able to change their shape. These cells also have the ability to secrete the extracellular matrix, which expresses proteins and cytokines, and are capable of phagocytosis and autophagy. The cytoskeleton is attached to the nuclear membrane and can, in millionths of a second, send signals to the nucleus in order to alter the expression of genes in an attempt to adapt to biomechanical insult. Oxidative stress, as happens in aging, has a deleterious effect on the TM, leading eventually to cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility, and (ultimately) increased IOP. TM failure is the most relevant factor in the cascade of events triggering apoptosis in the inner retinal layers, including ganglion cells. J. Cell. Physiol. 231: 1876-1893, 2016. © 2016 Wiley Periodicals, Inc.

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Mechanotransduction Channels of the Trabecular Meshwork

Abstract: We demonstrated the presence of 11 mechanotransduction channels in the TM and in isolated TM cells at protein level. Demonstration of these channels as proteins at tissue and cellular level will pave the way for further experimentation.

Cited by 29 publications

References 55 publications

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Autophagy and mechanotransduction in outflow pathway cells

The Outflow Pathway: A Tissue With Morphological and Functional Unity

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