Keeping an Eye on Myocilin: A Complex Molecule Associated with Primary Open-Angle Glaucoma Susceptibility

Abstract

MYOC encodes a secretary glycoprotein of 504 amino acids named myocilin. MYOC is the first gene to be linked to juvenile open-angle glaucoma (JOAG) and some forms of adult-onset primary open-angle glaucoma (POAG). The gene was identified as an up-regulated molecule in cultured trabecular meshwork (TM) cells after treatment with dexamethasone and was originally referred to as trabecular meshwork-inducible glucocorticoid response (TIGR). Elevated intraocular pressure (IOP), due to decreased aqueous outflow, is the strongest known risk factor for POAG. Increasing evidence showed that the modulation of the wild-type (wt) myocilin protein expression is not causative of glaucoma while some misfolded and self-assembly aggregates of mutated myocilin may be associated with POAG in related or unrelated populations. The etiology of the disease remains unclear. Consequently, a better understanding of the molecular mechanisms underlyingPOAG is required to obtain early diagnosis, avoid potential disease progression, and develop new therapeutic strategies. In the present study, we review and discuss the most relevant studies regarding structural characterizations, expressions, molecular interactions, putative functions of MYOC gene and/or its corresponding protein in POAG etiology.

Thermally labile components of aqueous humor potently induce osteogenic potential in adipose-derived mesenchymal stem cells

“…The primary outflow pathway of AH is the trabecular meshwork (Gottanka et al, 1997; Johnson, 2006; Lutjen-Drecoll, 2005; Rohen et al, 1993), calcification of which has been implicated in glaucoma (Borras and Comes, 2009; Gonzalez et al, 2004; Gonzalez et al, 2000; Vittitow and Borras, 2004; Xue et al, 2007; Xue et al, 2006). This is consistent with glaucoma-associated increased AH expression of molecules linked to calcification, such as growth factor like lipids (Iyer et al, 2012; Liu et al, 2010), myocilin (Howell et al, 2010; Jacobson et al, 2001; Menaa et al, 2011; Nguyen et al, 1998; Polansky et al, 1997; Rao et al, 2000; Russell et al, 2001; Tamm, 2002), and connective tissue growth factor (Browne et al, 2011; Ho et al, 2005; Junglas et al, 2012; Junglas et al, 2009). In healthy meshwork, the activity of these stimulators of calcification is likely inhibited by the high expression of proteins such as matrix Gla protein (Gonzalez et al, 2004; Gonzalez et al, 2000; Tomarev et al, 2003; Vittitow and Borras, 2004).…”

Mutation Analysis of Seven Known Glaucoma-Associated Genes in Chinese Patients With Glaucoma

“…MYOC was the first identified gene associated with JOAG, and the mutation frequency ranged from 10--30% in previous studies. 20 In our study, the overall mutation frequency of MYOC in JOAG was 5.8% (6/104), while a mutation frequency of 12.5% was reported in a Taiwanese study, in which the mutations were detected in six of 48…”

“…8 MYOC has been confirmed to be associated with JOAG and POAG with different mutation frequencies in different ethnic groups. 20 Variants of OPA1 are associated with normal tension glaucoma (NTG). 14 A study of Japanese patients further implied that OPA1 affected the phenotypic features of patients with high tension glaucoma.…”

Using genetic mouse models to gain insight into glaucoma: Past results and future possibilities

“…Mutations in the myocilin gene ( MYOC ) cause ocular hypertension and glaucoma (Menaa et al, 2011; Stone et al, 1997). In humans and mice, MYOC is expressed in numerous ocular tissues, most notably in trabecular meshwork (TM) cells (for a review see; Resch and Fautsch, 2009).…”