Regulation of TIGR/MYOC gene expression in human trabecular meshwork cells

Polansky, Jon R.; Fauss, Donald J.; Zimmerman, C. C.

doi:10.1038/eye.2000.137

Cited by 82 publications

(63 citation statements)

References 32 publications

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“…Hypothesized roles of myocilin include increased resistance of aqueous outflow through the trabecular meshwork with subsequent IOP elevation 31,33 and effects on optic nerve myelination 34 thus glaucomatous damage. Stress, mechanical perturbations, and steroid treatment induces myocilin expression, 33,35,36 but endogenous protective regulators, such as basic fibroblast growth factor (bFGF) and T3 but not thyroxine (T4), have recently been shown to reduce myocilin production in human trabecular meshwork cell culture systems. 35 No adverse effects of synthetic thyroxine on the human eye have been reported in pharmacology literature.…”

Section: Discussionmentioning

confidence: 99%

“…Stress, mechanical perturbations, and steroid treatment induces myocilin expression, 33,35,36 but endogenous protective regulators, such as basic fibroblast growth factor (bFGF) and T3 but not thyroxine (T4), have recently been shown to reduce myocilin production in human trabecular meshwork cell culture systems. 35 No adverse effects of synthetic thyroxine on the human eye have been reported in pharmacology literature. 27,37 In frogs, the normal development of the ipsilateral retinothalamic projections 38 is inhibited by propylthiouracil and restored by the intraocular injection of thyroxine.…”

Section: Discussionmentioning

confidence: 99%

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Open-angle glaucoma and systemic thyroid disease in an older population: The Blue Mountains Eye Study

Lee

Rochtchina

Wang

et al. 2004

Eye

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Purpose To assess whether thyroid disease is independently associated with open-angle glaucoma (OAG), using history of thyroid disease and current thyroxine use. Methods The Blue Mountains Eye Study examined 3654 persons, aged 49-97 years. Interviewers collected self-reported history of diagnosis and treatment for thyroid disease. Eye examinations included applanation tonometry, stereoscopic optic disc photography and automated perimetry. OAG was diagnosed from the presence of matching typical glaucomatous field changes and optic disc cupping, independent of intraocular pressure. Associations between thyroid disease (history and treatment) and OAG were assessed in a multivariate model. Results Of 324 participants (8.9%) reporting history of thyroid disease, 147 (4.0%) were currently using thyroxine. Although we could not accurately categorize the thyroid disorder for all cases, current use of thyroxine suggests a prior hypothyroid state. All thyroid disease subgroups affected women more frequently than men, P ¼ 0.001. OAG was diagnosed in 108 subjects (3.0%) and was more frequent in those reporting past thyroid disease (4.6 vs 2.8%). This relationship was not statistically significant after adjusting for potential confounders, multivariate odds ratio (OR) 1.6; 95% confidence interval (95% CI) 0.9-2.9. OAG was significantly more frequent, however, in subjects reporting current thyroxine use (6.8 vs 2.8%), multivariate OR 2.1; 95% CI 1.0-4.4, or history of thyroid surgery (6.5 vs 2.8%), multivariate OR 2.5; 95% CI 1.0-6.2.Conclusions This population-based study suggests that thyroid disease, indicated by current thyroxine use or past thyroid surgery, could be independently related to OAG.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Open-angle glaucoma and systemic thyroid disease in an older population: The Blue Mountains Eye Study

Lee

Rochtchina

Wang

et al. 2004

Eye

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“…MYOC expression and OHT induction occur in response to GCs, and both follow similar time-course and dose-response curves. 26,60,61 Few studies have addressed the potential role of myocilin in GC-induced OHT. Both Shepard et al 62 and Kirstein et al 63 showed that myocilin induction by GCs was because of other transcription factors or remote glucocorticoid response elements and not by sequences in the proximal region of the myocilin gene promoter.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone-Induced Ocular Hypertension in Mice

Patel

Phan

Maddineni

et al. 2017

The American Journal of Pathology

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Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious adverse effect of prolonged GC therapy that can lead to iatrogenic glaucoma and permanent vision loss. An appropriate mouse model can help us understand precise molecular mechanisms and etiology of GC-induced OHT. We therefore developed a novel, simple, and reproducible mouse model of GC-induced OHT. GC-induced myocilin expression in the trabecular meshwork (TM) has been suggested to play an important role in GC-induced OHT. We further determined whether myocilin contributes to GC-OHT. C57BL/6J mice received weekly periocular conjunctival fornix injections of a dexamethasone-21-acetate (DEX-Ac) formulation. Intraocular pressure (IOP) elevation was relatively rapid and significant, and correlated with reduced conventional outflow facility. Nighttime IOPs were higher in ocular hypertensive eyes compared to daytime IOPs. DEX-Ac treatment led to increased expression of fibronectin, collagen I, and a-smooth muscle actin in the TM in mouse eyes. No changes in body weight indicated no systemic toxicity associated with DEX-Ac treatment. Wild-type mice showed increased myocilin expression in the TM on DEX-Ac treatment. Both wild-type and Myoc À/À mice had equivalent and significantly elevated IOP with DEX-Ac treatment every week. In conclusion, our mouse model mimics many aspects of GC-induced OHT in humans, and we further demonstrate that myocilin does not play a major role in DEX-induced OHT in mice. (Am J Pathol 2017, 187: 713e723; http://dx.doi.org/10.1016/j.ajpath.2016 Glucocorticoids (GCs) are one of the most commonly prescribed medications worldwide for the treatment of a plethora of diseases and conditions. Because of their broadspectrum anti-inflammatory and immunosuppressive properties, the worldwide market for GC use is estimated to be >$10 billion per year.1 Approximately 1.2% of US and 0.85% of UK populations are prescribed therapeutic GCs every year.2,3 GCs also remain the mainstay of treatment for a variety of ocular inflammatory diseases involving almost all tissues of the eye, such as eyelids, conjunctiva, cornea, sclera, uvea, retina, and optic nerve. 4 The routes of GC administration in treatment of these disorders can be topical ocular, oral, systemic, intravitreal injections and implants, and periocular injections (including subconjunctival, subtenon, retrobulbar, and peribulbar).5 However, prolonged GC therapy is associated with serious ocular adverse effects, including development of posterior subcapsular cataracts, and the development of GC-induced ocular hypertension (GC-OHT) and iatrogenic open-angle glaucoma.The clinical presentation of GC-induced glaucoma is similar to primary open-angle glaucoma (POAG), and for >50 years, reports have suggested a link between glaucoma and GCs. Development of GC-induced OHT depends on GC dose and duration of treatment, method of administration, potency of GC, and individual susceptibility to GCs. 6e8 There are varying degrees of steroid responsiveness (ie, development of GC-OHT) among individ...

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“…(Clark et al 1995b;Clark et al 2005) Much of this effect may be due to dramatic cytoskeleton changes, i.e., the formation of cross-linked actin networks (CLANs) (Clark et al 1994;Clark et al 1995a), or to a number of other TM cell responses, e.g., increased expression of myocilin. (Polansky et al 1997;Stone et al 1997;Polansky and Nguyen 1998;Polansky et al 2000;Lo et al 2003) Myocilin has been shown to affect outflow facility, although the exact mechanism appears to be complex. (Borras et al 2002;Goldwich et al 2003;Zillig et al 2005; Myocilin also binds several ECM components, including the hep II domain of fibronectin, (Filla et al 2002) and is found in the JCT and SC region.…”

Section: Tgfβmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

424

443

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The extracellular matrix (ECM) of the trabecular meshwork (TM) is thought to be important in regulating intraocular pressure (IOP) in both normal and glaucomatous eyes. IOP is regulated primarily by a fluid resistance to aqueous humor outflow. However, neither the exact site nor the identity of the normal resistance to aqueous humor outflow has been established. Whether the site and nature of the increased outflow resistance, which is associated with open-angle glaucoma, is the same or different from the normal resistance is also unclear.The ECMs of the TM beams, juxtacanalicular region (JCT) and Schlemm's canal (SC) inner wall are comprised of fibrillar and non-fibrillar collagens, elastin-containing microfibrils, matricellular and structural organizing proteins, glycosaminoglycans (GAGs) and proteoglycans. Both basement membranes and stromal ECM are present in the TM beams and JCT region. Cell adhesion proteins, cell surface ECM receptors and associated binding proteins are also present in the beams, JCT and SC inner wall region.The outflow pathway ECM is relatively dynamic, undergoing constant turnover and remodeling. Regulated changes in enzymes responsible for ECM degradation and biosynthetic replacement are observed. IOP homeostasis, triggered by pressure changes or mechanical stretching of the TM, appears to involve ECM turnover. Several cytokines, growth factors and drugs, which affect the outflow resistance, change ECM component expression, mRNA alternative splicing, cellular cytoskeletal organization or all of these. Changes in ECM associated with open-angle glaucoma have been identified.

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Regulation of TIGR/MYOC gene expression in human trabecular meshwork cells

Cited by 82 publications

References 32 publications

Open-angle glaucoma and systemic thyroid disease in an older population: The Blue Mountains Eye Study

Open-angle glaucoma and systemic thyroid disease in an older population: The Blue Mountains Eye Study

Dexamethasone-Induced Ocular Hypertension in Mice

Extracellular matrix in the trabecular meshwork

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