Association of POAG Risk Factors and the Thr377Met<i>MYOC</i>Mutation in an Isolated Greek Population

Wirtz, Mary K.; Samples, John R.; Toumanidou, Victoria; Charlesworth, Jac; Mikropoulos, Dimitrios G.; Kaltsos, K.; Economou, A. S.; Dimopoulos, A. T.; Georgiadou, I.; Moumtzis, G.; Papanastasiou, Athanasios; Kramer, Patricia L.; Dyer, Tom; Blangero, John; Konstas, Anastasios G. P.

doi:10.1167/iovs.09-4652

Cited by 5 publications

(1 citation statement)

References 32 publications

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“…Myocilin is a member of the olfactomedin protein family with an N-terminal leucine zipper motif and a large C-terminal olfactomedin homology domain (Box 2). Association studies and analyses of pedigrees have shown that mutations in myocilin, especially its olfactomedin domain, are associated with a substantial fraction (>10 %) of juvenile onset glaucoma patients [2,6,7] and a smaller portion (~4%) of adult POAG cases in African-American [8], Canadian [9], Indian [10], Japanese [11], Greek [12], South African [13], Brazilian [14], Peruvian [15], Ghanaian [16], Swiss [17], and Dutch [18] populations. However, in some populations, including Moroccan [19], Middle Eastern [20], and Finnish populations [21], case-control studies failed to identify POAG-associated polymorphisms in myocilin.…”

Section: Glaucoma and Myocilinmentioning

confidence: 99%

A molecular mechanism for glaucoma: endoplasmic reticulum stress and the unfolded protein response

Anholt

Carbone

2013

Trends in Molecular Medicine

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Primary open angle glaucoma (POAG) is a common late-onset neurodegenerative disease. Ocular hypertension represents a major risk factor, but POAG etiology remains poorly understood. Some cases of early-onset congenital glaucoma and adult POAG are linked to mutations in myocilin, a secreted protein of poorly defined function. Transgenic overexpression of myocilin in Drosophila and experiments in mice and human populations implicate the unfolded protein response (UPR) in the pathogenesis of glaucoma. We postulate that compromised ability of the UPR to eliminate misfolded mutant or damaged proteins, including myocilin, causes endoplasmic reticulum stress, resulting in functional impairment of trabecular meshwork cells that regulate intraocular pressure. This mechanism of POAG is reminiscent of other age-dependent neurodegenerative diseases that involve accumulation of protein aggregates.

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