Biological properties of trabecular meshwork cells

Gasiorowski, Joshua Z.; Russell, Paul

doi:10.1016/j.exer.2008.08.006

Cited by 57 publications

(44 citation statements)

References 41 publications

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“…For this reason, HTM cells have been used in vitro to investigate mechanisms by which HTM cells are altered during disease. A commonly used in vitro model for glaucoma is treatment of HTM cells with glucocorticoids (GCs), 20 a family of steroid hormones. Approximately 30% to 40% of people treated with GCs develop elevated IOP (referred to as steroid responders), and this is a causal risk factor for glaucoma.…”

mentioning

confidence: 99%

Role of Substratum Stiffness in Modulating Genes Associated with Extracellular Matrix and Mechanotransducers YAP and TAZ

Raghunathan

Morgan

Dreier

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Primary open-angle glaucoma is characterized by increased resistance to aqueous humor outflow and a stiffer human trabecular meshwork (HTM). Two Yorkie homologues, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif, encoded by WWTR1 (TAZ), are mechanotransducers of the extracellular-microenvironment and coactivators of transcription. Here, we explore how substratum stiffness modulates the YAP/TAZ pathway and extracellular matrix genes in HTM cells and how this may be play a role in the onset and progression of glaucoma.METHODS. HTM cells from normal donors were cultured on hydrogels mimicking the stiffness of normal (5 kPa) and glaucomatous (75 kPa) HTM. Changes in expression of YAP/ TAZ related genes and steroid responsiveness were determined. Additionally, transglutaminase-2 expression was determined after YAP silencing.RESULTS. YAP and TAZ are both expressed in human trabecular meshwork cells. In vitro, YAP and TAZ were inversely regulated by substratum stiffness. YAP and 14-3-3r were downregulated to different extents on stiffer substrates; TAZ, tissue transglutaminase (TGM2), and soluble frizzled-related protein-1 (sFRP-1) were significantly upregulated. CTGF expression appeared to be altered differentially by both YAP and TAZ. Myocilin and angiopoietin-like 7 expression in response to dexamethasone was more pronounced on stiffer substrates. We demonstrated a direct effect by YAP on TGM2 when YAP was silenced by small interfering RNA.CONCLUSIONS. The expression of YAP/TAZ and ECM-relatedgenes is impacted on physiologically relevant substrates. YAP was upregulated in cells on softer substrates. Stiffer substrates resulted in upregulation of canonical Wnt modulators, TAZ and sFRP-1, and thus may influence the progression of glaucoma. These results demonstrate the importance of YAP/TAZ in the HTM and suggest their role in glaucoma. (Invest Ophthalmol Vis Sci.

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confidence: 99%

Role of Substratum Stiffness in Modulating Genes Associated with Extracellular Matrix and Mechanotransducers YAP and TAZ

Raghunathan

Morgan

Dreier

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…32,33 Primary TM cells are usually obtained from donor human eyes, and culturing of GTM cells from glaucomatous TM is more demanding. 29,34,35 Since primary cells grow very slowly and stop proliferating after a few passages, only limited amounts of cells are available. Besides, it was reported that TM cells in primary culture could be "activated" in vitro with an increasing amount of mitochondria, compared with normal TM cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic oxidative stress induced by H 2 O 2 treatment or hyperoxia (40% oxygen) is one of the common methods in TM cell-based glaucoma models in vitro. 29 H 2 O 2 is a key oxidant and a normal constituent that presents in approximately 25-70 M in the aqueous humor. 30,31 It has been reported that TM cells were exposed to high concentration of ROS and H 2 O 2 in patients with POAG.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria-Targeted Peptide MTP-131 Alleviates Mitochondrial Dysfunction and Oxidative Damage in Human Trabecular Meshwork Cells

Chen

Liu

Gao

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the antioxidative ability of a novel mitochondria-targeted peptide MTP-131 in immortalized human trabecular meshwork (iHTM) and glaucomatous human trabecular meshwork (GTM 3 ) cell lines. METHODS. Cultured iHTM and GTM 3 cells were pretreated with MTP-131 for 1 hour, and sustained oxidative stress was induced by subjecting TM cells to 200 M hydrogen peroxide (H 2 O 2 ) for 24 hours. Untreated cells and cells incubated with H 2 O 2 alone were used as controls. Lactate dehydrogenase (LDH) assay was used to determine cell viability. Changes of mitochondrial membrane potential (⌬⌿m) and generation of intracellular reactive oxygen species (ROS) were analyzed by flow cytometry and confocal microscopy. Activation of caspase 3 was quantified by Western blotting, and apoptosis was measured by flow cytometry. Release of cytochrome c and changes in cytoskeleton were analyzed by confocal microscopy. Data were analyzed with commercial data analysis software and P Ͻ 0.05 was considered to be statistically significant. RESULTS. In both iHTM and GTM 3 cells, decrease of ⌬⌿m and elevation of intracellular ROS were detected after sustained oxidative stress induced by H 2 O 2 . When cells were pretreated with MTP-131, the H 2 O 2 -induced mitochondrial depolarization was prevented; intracellular ROS, LDH release, and apoptosis were significantly decreased; release of cytochrome c from mitochondria to cytoplasm and activation of caspase 3 were inhibited. In addition, cytoskeleton changes caused by H 2 O 2 were also alleviated by MTP-131. CONCLUSIONS. Mitochondria-targeted peptide MTP-131 could prevent both iHTM and GTM 3 cells from sustained oxidative stress induced by H 2 O 2 . (Invest Ophthalmol Vis Sci. 2011;52: 7027-7037)

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“…35 TM cells respond to mechanical strain increasing ECM turnover, altered gene expression, and release of several cytokines. 45 TM cells have phagocytic properties, 46,47 and with age they tend to engulf melanin granules released by the posterior surface of the iris (Fig. 5).…”

Section: Trabecular Outflowmentioning

confidence: 99%

Functional Anatomy of the Outflow Facilities

Pizzirani

Gong

2015

Veterinary Clinics of North America: Small Animal Practice

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The aqueous humor (AH) is the fluid that fills the anterior and posterior chambers of the eye. Its main roles are to provide nourishment and metabolic waste removal to active metabolic ocular structures that are avascular and to contribute maintaining a normal intraocular pressure (IOP) without altering the refractive status of the eye. Its composition and the fluid dynamics associated with its flow are voluble and undergo changes associated with age and disease. Of particular importance is that the resistance to the outflow of AH from the anterior chamber is influenced by morphologic, physiologic, and biochemical dynamic factors.1 Beside aqueous nutritional importance, its solutes also participate in establishing the anterior chamber associate immune deviation, and carry and distribute the different proteins and molecules that promote and direct tissue remodeling and changes in the anterior segment that are associated with both age and disease.

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Biological properties of trabecular meshwork cells

Cited by 57 publications

References 41 publications

Role of Substratum Stiffness in Modulating Genes Associated with Extracellular Matrix and Mechanotransducers YAP and TAZ

Role of Substratum Stiffness in Modulating Genes Associated with Extracellular Matrix and Mechanotransducers YAP and TAZ

Mitochondria-Targeted Peptide MTP-131 Alleviates Mitochondrial Dysfunction and Oxidative Damage in Human Trabecular Meshwork Cells

Functional Anatomy of the Outflow Facilities

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