Analysis of adult Tg-MYOC(Y437H) mice, which we showed express human MYOC containing the Y437H mutation within relevant eye tissues, revealed that they display glaucoma phenotypes (i.e., elevated intraocular pressure [IOP], retinal ganglion cell death, and axonal degeneration) closely resembling those seen in patients with POAG caused by the Y437HMYOC mutation.
Among POAG patients, there were no differences in mean C/D ratio, IOP, number of glaucoma medications, and surgical procedures for IOP control between carries and non-carriers of the MYOC mt.1 promoter polymorphism (p>0.05).
After significant surgical reduction of IOP by TE, there are no significant detectable morphological changes in the ONH or the ganglion cell complex as measured by OCT, nor does the papillary or macular OCTA-determined VD change significantly.
In contrast to previous reports, a Gln368Stop mutation of the GLC1A gene need not be confined to patients with glaucomatous optic atrophy due to high IOP.
Variants of myocilin, localized to its olfactomedin (OLF) domain, have been linked to inherited forms of glaucoma, a disease associated with elevated intraocular pressure.
Peak intraocular pressure (IOP) did not differ significantly between the two groups of families, while linkage to GLC1A conferred a highly increased risk of developing OAG and of having severe glaucomatous optic neuropathy.
Several of these myocilin mutations were observed in multiple patients allowing the identification of mutation-specific glaucoma phenotypes (maximum intraocular pressure and age at diagnosis).
The prevalence of Myocilin mutations rose from 16% to 40% in selected advanced POAG subgroups based on different thresholds of maximum recorded intraocular pressure, age at diagnosis, and the presence and strength of positive family history.
Characterization of cat myocilin will enable long-term studies be performed in Felix domesticus to analyze changes to intraocular pressure and the aqueous outflow pathway following expression of myocilin and glaucoma causing mutations.
Inclusion of the myocilinQ368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci.
The block of myocilin secretion was proposed to alter the extracellular matrix environment of the trabecular meshwork, with subsequent impediment of aqueous humor outflow leading to elevated intraocular pressure.
Meox2 haploinsufficiency did not affect the characteristic diseases of the iris or IOP elevation seen in DBA/2J mice but did cause a significant increase in the numbers of eyes with axon damage compared to controls.
Glaucoma in this family has a later average age at diagnosis and significantly less elevation in intraocular pressure than GLC1A glaucoma so far described.
In this recently identified protein misfolding disorder, aggregation-prone disease variants of myocilin hasten glaucoma-associated elevation of intraocular pressure, leading to vision loss.
DBA/2J mice exhibit elevated intraocular pressure, progressive degeneration of their retinal ganglion cells, and optic neuropathy that resembles glaucoma.
We will review the current understanding of myocilin with special emphasis on the structural makeup of the myocilin gene and protein, its possible physiological roles internal and external to ocular cells, the regulation of intraocular pressure as evidenced through the use of perfusion culture systems and animal models, and as a causative agent in some forms of glaucoma.
To directly test if increased levels of MYOC can cause IOP elevation and glaucoma, we generated bacterial artificial chromosome transgenic mice that overexpress Myoc at a level similar to that induced by corticosteroid use.
On the other hand, there were significant changes in the purinergic receptor expression in DBA/2J suggesting that elevated IOP in these animals could be related to an increase of P2Y<sub>2</sub> expression and a decrease in P2Y<sub>1</sub> receptors.
We show in DBA/2J mice with spontaneous IOP elevation and glaucoma that the lifespan of functional RGCs can be extended by preconditioning RGCs with retrobulbar lidocaine in one eye at four months of age that temporary blocks RGC axonal transport.
The GLC1AThr377Met mutation is associated with POAG that, in the pedigrees studied, had a younger age at onset and higher peak intraocular pressure than in pedigrees with the more common Gln368STOP mutation.