Another Piece of the Puzzle: MYOC and Myocilin Glaucoma

Fini, M. Elizabeth

doi:10.1167/iovs.17-23045

Cited by 5 publications

(8 citation statements)

References 4 publications

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“…Recently, the crystal structure of myocilin-OLF was elucidated, and it indicated that myocilin-OLF belongs to the five-bladed β-propeller family (108), which is a known hub for protein-protein interactions. To date, a number of extracellular proteins interacting with myocilin have been identified, including tissue inhibitor of matrix metalloproteinase (TIMP3) (8,50), fibronectin (107), flotillin-1 (109) and hevin (46).…”

Section: Imbalance Of Pathogenic Myocilin and Extracellular Proteinsmentioning

confidence: 99%

“…Notably, MMP2 activity may be associated with the regulation of IOP, which may be predominantly associated with the TM, where myocilin and TIMP3 coexist (50). MMP2, which is abundant in the TM (8), is involved in the breakdown of extracellular matrix (52), which facilitates aqueous humor outflow (8). It has also been demonstrated that myocilin mutations or MYOC null can enhance inhibition of MMP2 by TIMP3 (8,50).…”

Section: Imbalance Of Pathogenic Myocilin and Extracellular Proteinsmentioning

confidence: 99%

“…MMP2, which is abundant in the TM (8), is involved in the breakdown of extracellular matrix (52), which facilitates aqueous humor outflow (8). It has also been demonstrated that myocilin mutations or MYOC null can enhance inhibition of MMP2 by TIMP3 (8,50). An imbalance between MMPs and TIMP within the TM can cause POAG (113).…”

Section: Imbalance Of Pathogenic Myocilin and Extracellular Proteinsmentioning

confidence: 99%

“…The pathogenesis of glaucoma remains unknown; however, accumulating evidence indicates that genetic factors may play a causative role (7). The myocilin gene (MYOC), which encodes the secreted protein myocilin, is the first and most extensively investigated gene associated with familial forms of POAG (8,9). MYOC is detected in the aqueous humor and MYOC mutations are the most common type of mutation in patients with glaucoma (10), accounting for 10% of juvenile-onset open-angle glaucoma (JOAG) (11) and 2-4% of adult-onset POAG (12).…”

Section: Introductionmentioning

confidence: 99%

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Physiological function of myocilin and its role in the pathogenesis of glaucoma in the trabecular meshwork (Review)

Wang

Zhang

et al. 2018

Int J Mol Med

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Myocilin is highly expressed in the trabecular meshwork (TM), which plays an important role in the regulation of intraocular pressure (IOP). Myocilin abnormalities may cause dysfunction of the TM, potentially leading to increased IOP. High IOP is a well-known primary risk factor for glaucoma. Myocilin mutations are common among glaucoma patients, and they are implicated in juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (POAG). Aggregation of aberrant mutant myocilins is closely associated with glaucoma pathogenesis. The aim of the present review was to discuss the recent findings regarding the major physiological functions of myocilin, such as intra- and extracellular proteolytic processes. We also aimed to discuss the risk factors associated with myocilin and the development of glaucoma, such as misfolded/mutant myocilin, imbalance of myocilin and extracellular proteins, and instability of mutant myocilin associated with temperature. Finally, we further outlined certain issues that are yet to be resolved, which may represent the basis for future studies on the role of myocilin in glaucoma.

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Section: Imbalance Of Pathogenic Myocilin and Extracellular Proteinsmentioning

confidence: 99%

Section: Imbalance Of Pathogenic Myocilin and Extracellular Proteinsmentioning

confidence: 99%

Section: Imbalance Of Pathogenic Myocilin and Extracellular Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Physiological function of myocilin and its role in the pathogenesis of glaucoma in the trabecular meshwork (Review)

Wang

Zhang

et al. 2018

Int J Mol Med

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“…Previous genome-wide association studies identified over 10 genes associated with primary open-angle glaucoma, including myocilin (MYOC), optineurin (OPTN ) and WD repeat domain 36 (WDR36 ) (Liu & Allingham, 2017). Mutations in MYOC cause a cascade of abnormalities in the trabecular meshwork, including the intracellular retention of myocilin, reduced aqueous outflow, increased IOP, and glaucoma (Fini, 2017). Optineurin regulates many physiological processes, including membrane trafficking, protein secretion, cell division, autophagy, and host defense against pathogens (Kachaner et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Expression profile analysis to predict potential biomarkers for glaucoma: BMP1, DMD and GEM

Zhang

2020

PeerJ

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Purpose Glaucoma is the second commonest cause of blindness. We assessed the gene expression profile of astrocytes in the optic nerve head to identify possible prognostic biomarkers for glaucoma. Method A total of 20 patient and nine normal control subject samples were derived from the GSE9944 (six normal samples and 13 patient samples) and GSE2378 (three normal samples and seven patient samples) datasets, screened by microarray-tested optic nerve head tissues, were obtained from the Gene Expression Omnibus (GEO) database. We used a weighted gene coexpression network analysis (WGCNA) to identify coexpressed gene modules. We also performed a functional enrichment analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Genes expression was represented by boxplots, functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all the key genes. Then the key genes were validated by the external dataset. Results A total 8,606 genes and 19 human optic nerve head samples taken from glaucoma patients in the GSE9944 were compared with normal control samples to construct the co-expression gene modules. After selecting the most common clinical traits of glaucoma, their association with gene expression was established, which sorted two modules showing greatest correlations. One with the correlation coefficient is 0.56 (P = 0.01) and the other with the correlation coefficient is −0.56 (P = 0.01). Hub genes of these modules were identified using scatterplots of gene significance versus module membership. A functional enrichment analysis showed that the former module was mainly enriched in genes involved in cellular inflammation and injury, whereas the latter was mainly enriched in genes involved in tissue homeostasis and physiological processes. This suggests that genes in the green–yellow module may play critical roles in the onset and development of glaucoma. A LASSO regression analysis identified three hub genes: Recombinant Bone Morphogenetic Protein 1 gene (BMP1), Duchenne muscular dystrophy gene (DMD) and mitogens induced GTP-binding protein gene (GEM). The expression levels of the three genes in the glaucoma group were significantly lower than those in the normal group. GSEA further illuminated that BMP1, DMD and GEM participated in the occurrence and development of some important metabolic progresses. Using the GSE2378 dataset, we confirmed the high validity of the model, with an area under the receiver operator characteristic curve of 85%. Conclusion We identified several key genes, including BMP1, DMD and GEM, that may be involved in the pathogenesis of glaucoma. Our results may help to determine the prognosis of glaucoma and/or to design gene- or molecule-targeted drugs.

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