Mutations in each of three genes, myocilin (MYOC), optineurin (OPTN), and TANK binding kinase 1 (TBK1), may cause primary open-angle glaucoma (POAG) that is inherited as a Mendelian trait.
In this study, we investigated the involvement of the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway, two major intracellular protein quality control systems, in the regulation of wild-type (WT) OPTN, ALS-linked mutant E478GOPTN and POAG-linked mutant E50KOPTN.
With well-established role of genes like Myocilin (MYOC), Optineurin (OPTN) and WD repeat Domain 36, (WDR36), at least 29 genetic loci have been found till date to be linked to POAG.
The present study was designed to identify lncRNAs associated with OPTN (E50K) transgenic mice and investigate its functions in the pathogenesis of POAG.
The myocilin (MYOC) and optineurin (OPTN) genes were directly sequenced in 112 unrelated patients, including 17 with primary open‑angle glaucoma, 19 with juvenile open‑angle glaucoma, and 76 with normal tension glaucoma.
Autosomal dominantly inherited OPTN mutations have been described as a cause of primary open-angle glaucoma in the Netherlands and were also found in two Dutch sporadic MND patients.
The E50Koptineurin transgenic mouse described here exhibited clinical features of POAG and may be useful for mechanistic dissection of POAG and therapeutic development.
Optineurin, a cytosolic protein associated with the actin cytoskeleton, microtubules, and the Golgi complex, appears to have an important function in neurons, as mutations in its gene are causative for neurodegenerative diseases such as primary open-angle glaucoma and amyotrophic lateral sclerosis.
Optineurin (OPTN) is a multifunctional protein and its mutations are associated with neurodegenerative diseases such as POAG and amyotrophic lateral sclerosis (ALS).
Optineurin (OPTN) is a multifunctional protein and its mutations are associated with neurodegenerative diseases such as POAG and amyotrophic lateral sclerosis (ALS).
POAG links to at least 20 genetic loci, but only 2 genes identified in these loci, myocilin and optineurin, are considered as well-established glaucoma-causing genes, whereas the role of other loci, genes, and variants implicated in the development of POAG remains controversial.
Furthermore, there is growing evidence for an association of Optn mutations with human diseases such as primary open-angle glaucoma, amyotrophic lateral sclerosis and Paget's disease of bone.
About 5% of primary open angle glaucoma (POAG) is currently attributed to single-gene or Mendelian forms of glaucoma (ie glaucoma caused by mutations in myocilin or optineurin).
Analysis of cell transfection showed that the nonsense and missense mutations of OPTN abolished the inhibition of activation of nuclear factor kappa B (NF-kappaB), and the E478G mutation revealed a cytoplasmic distribution different from that of the wild type or a POAG mutation.