Dexamethasone-Associated Cross-Linked Actin Network Formation in Human Trabecular Meshwork Cells Involves β3 Integrin Signaling

Filla, Mark S.; Schwinn, Marie K.; Nosie, Amanda K.; Clark, Ross; Peters, Donna M.

doi:10.1167/iovs.10-6618

Cited by 83 publications

(128 citation statements)

References 30 publications

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“…This lack of colocalization contrasted with filamin A whose localization completely mirrored F-actin labeling in earlier studies (5). Overall, DEX increased CLAN formation in TM cells as previously reported [13] from 3 Ϯ 3% in ethanol-treated cells to 10 Ϯ 5% in DEX-treated cells (p Ͻ 0.0001).…”

Section: Fig 2 Distribution Of Proteins In Htm Culturessupporting

confidence: 83%

“…It has been previously shown that activation of ␤3 integrin can trigger CLAN formation in nonglaucomatous cells (4,5), and that this protein is up-regulated and activated on the cell surface following DEX treatment (13). Previous work has also shown that treatment with the PI-3 kinase inhibitor LY294002 significantly decreased CLAN formation (4).…”

Section: Discussionmentioning

confidence: 98%

“…Spreading Assays and Immunofluorescence Microscopy-Confluent HTM monolayers pretreated with either DEX or ethanol for 5-7 days were serum-starved for 24 h and then replated in the continued presence of DEX or ethanol onto coverslips precoated with 20 nM fibronectin as previously described (4,5,13). Cells were allowed to spread for 3 h before fixation/permeablization in 4% p-formaldehyde plus 0.18% TX-100 for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have suggested that DEX up-regulates and activates a ␤3 integrin signaling pathway that induces CLAN formation (13). This signaling cascade includes Src, the Rho family GTPase Rac1, and the Rac1 guanine nucleotide exchange factor (GEF) Trio (4).…”

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confidence: 99%

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Comparative Genomic and Proteomic Analysis of Cytoskeletal Changes in Dexamethasone-Treated Trabecular Meshwork Cells

Clark¹,

Nosie²,

Walker³

et al. 2013

Molecular & Cellular Proteomics

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Steroid-induced glaucoma is an iatrogenic condition resulting from the use of glucocorticoids. Glucocorticoids such as dexamethasone (DEX) 1 raise intraocular pressure (IOP) in ϳ40% of patients in the general population, and ϳ6% of these patients will go on to develop glaucoma (1, 2). This condition is similar to primary open angle glaucoma (1-3), and is caused by a restriction in fluid outflow through the trabecular meshwork (TM), resulting in an imbalance between the amount of aqueous humor produced and the amount drained. This imbalance results in a higher IOP.It is thought that an alteration in the cytoskeletal structure or contractile properties of TM cells may result in the disruption of normal fluid flow. In support of this idea, cross-linked actin networks, referred to as CLANs, have been observed with increased frequency in the TM of glaucomatous patients and in glucocorticoid treated anterior segments as well as in TM cells in culture. CLANs are thought to alter the contractility of the TM by holding the cells in a rigid conformation, making the cells unresponsive to the change in pressure and blocking the aqueous humor outflow pathway (1,4,5). Thus, agents such as H7 and the latrunculins A and B, which disrupt the organization of the cytoskeleton, decrease IOP in porcine and monkey cultured anterior segments (6 -9).Control of the actin cytoskeleton is mediated by the Rho family of small GTPases. The Rho effector ROCK has been shown to play a part in TM contractility and modulation of IOP. Inhibition of ROCK using a dominant negative mutant or the inhibitor Y-27632 causes TM cells to "relax" by decreasing actin stress fiber formation and phosphorylation of myosin light chain (MLC) (10, 11). ROCK inhibition also decreases IOP in cultured human and porcine anterior segments (10, 11). In contrast, constitutively active RhoA (RhoA V14) increases From the ‡Departments

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Section: Fig 2 Distribution Of Proteins In Htm Culturessupporting

confidence: 83%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Comparative Genomic and Proteomic Analysis of Cytoskeletal Changes in Dexamethasone-Treated Trabecular Meshwork Cells

Clark¹,

Nosie²,

Walker³

et al. 2013

Molecular & Cellular Proteomics

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“…Modulation of ECM composition that controls TM elasticity and compliance may be important to normal function [44]. Studies implicate changes in cell [45][46][47][48] and ECM stiffness as probable factors in the glaucoma process. Recent elastic modulus determination in normal and glaucoma has indicated a relationship of increased TM tissue stiffness to OAG [49][50][51], a change also suggested by clinical studies [52][53][54].…”

Section: Introductionmentioning

confidence: 99%

Pulsatile motion of the trabecular meshwork in healthy human subjects quantified by phase-sensitive optical coherence tomography

Shen

Johnstone

et al. 2013

Biomed. Opt. Express

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Aqueous leaves the anterior chamber of eye by passing through the trabecular meshwork (TM), a tissue thought to be responsible for increased outflow resistance in glaucoma. Motion assessment could permit characterization of TM biomechanical properties necessary to maintain intra-ocular pressure (IOP) within a narrow homeostatic range. In this paper, we report the first in vivo identification of TM motion in humans. We use a phase-sensitive optical coherence tomography (PhS-OCT) system with sub-nanometer sensitivity to detect and image dynamic pulse-induced TM motion. To permit quantification of TM motion and relationships we develop and apply a phase compensation algorithm permitting removal of the otherwise evitable confounding effects of bulk motion. Twenty healthy human eyes from 10 subjects are imaged. The results permit visualization of pulsatile TM motion visualization by PhS-OCT; correlation with the digital/cardiac pulse is highly significant. The correlation permits assessment of the phase lag and time delay between TM motion and the cardiac pulse. In this study, we find that the digital pulse leads the pulsatile TM motion by a mean phase of 3.53 ± 0.48 rad and a mean time of 0.5 ± 0.14 s in the fundamental frequency. A significant linear relationship is present between the TM phase lag and the heart rate (p value < 0.05). The TM phase lag is also affected by age, the relationship not quite reaching significance in the current study. PhS-OCT reveals pulse-induced motion of the TM that may provide insights into the biomechanics of the tissues involved in the regulation of IOP. 11052-11065 (2008). 14. X. Liang, S. G. Adie, R. John, and S. A. Boppart, "Dynamic spectral-domain optical coherence elastography for tissue characterization," Opt. Express 18(13), 14183-14190 (2010). 15. P. Li, A. Liu, L. Shi, X. Yin, S. Rugonyi, and R. K. Wang, "Assessment of strain and strain rate in embryonic chick heart in vivo using tissue Doppler optical coherence tomography," Phys. Med. Biol. 56 (22), 7081-7092 (2011). 16. P. Li, X. Yin, L. Shi, S. Rugonyi, and R. K. Wang, "In vivo functional imaging of blood flow and wall strain rate in outflow tract of embryonic chick heart using ultrafast spectral domain optical coherence tomography," J. ©2013 Optical Society of America

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One Health Approach for Eye Care

et al. 2023

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Dexamethasone-Associated Cross-Linked Actin Network Formation in Human Trabecular Meshwork Cells Involves β3 Integrin Signaling

Cited by 83 publications

References 30 publications

Comparative Genomic and Proteomic Analysis of Cytoskeletal Changes in Dexamethasone-Treated Trabecular Meshwork Cells

Comparative Genomic and Proteomic Analysis of Cytoskeletal Changes in Dexamethasone-Treated Trabecular Meshwork Cells

Pulsatile motion of the trabecular meshwork in healthy human subjects quantified by phase-sensitive optical coherence tomography

One Health Approach for Eye Care

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