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. MYOC mutations cause 3-4% of POAG cases with IOP >21 mmHg, while mutations in OPTN, TBK1, and MYOC each caus …

2023年5月15日 · Pathogenic variants in TBK1, MYOC, and OPTN are associated with primary open-angle glaucoma (POAG) with severe visual field defects. This study aims to understand further POAG-related pathogenic variant (s) based on a cohort of East Asian populations that have not been well-characterized.

TBK1, OPTN, and TLR4 each encode proteins that interact to activate autophagy. On the basis of these data, we hypothesize that mutations (such as a TBK1 gene duplication) may abnormally activate autophagy and lead to retinal ganglion cell death and glaucoma.

2019年9月1日 · Mutations myocilin (MYOC), optineurin (OPTN), and TANK binding kinase 1 (TBK1), may cause primary open-angle glaucoma (POAG) that is inherited as a Mendelian trait. MYOC mutations cause 3-4% of POAG cases with IOP > 21 mmHg. OPTN, TBK1, and MYOC each cause ∼1% of POAG with IOP ≤ 21 mmHg.

2018年6月6日 · Transgenic mice expressing E50K-OPTN show loss of RGCs and persistent reactive gliosis. TBK1 protein kinase, which mediates E50K-OPTN and M98K-OPTN induced cell death, is emerging as a potential drug target. Autoimmunity has been implicated in glaucoma but involvement of OPTN or its mutants in autoimmnity has not been explored.

2015年9月16日 · Tbk1-induced cell death possibly involves autophagy, as shown by the effect of Atg5 knockdown, and requirement of autophagic function of OPTN. Our results show that phosphorylation of Ser177 plays a crucial role in M98K-OPTN-induced autophagosome formation, autophagy flux and retinal cell death.

TBK1 inhibition has emerged as a potential therapy for NTG. In this manuscript, we focus on the OPTN E50K mutation, the most common mutation for NTG, to describe the molecular mechanism of NTG by expressing a mutant Optn gene in cells and genetically modified mice.

2013年5月12日 · The optineurin (OPTN) E50K mutation was first identified in familial primary open-angle glaucoma (POAG), the onset of which is not associated with intraocular pressure (IOP) elevation, and is classified as normal-tension glaucoma (NTG).

Specifically exploring optineurin (OPTN), TANK binding kinase 1 (TBK1), methyltransferase-like 23 (METTL23), and myocilin (MYOC) mutations, we summarize their clinical manifestations, mutant protein behaviors, relevant animal models, and potential therapeutic pathways.

2015年9月16日 · Here, we have explored the role of Tbk1 in M98K-OPTN-induced autophagy and cell death, and the effect of Tbk1 overexpression in retinal cells. Cell death induced by M98K-OPTN was dependent on Tbk1 as seen by the effect of Tbk1 knockdown and blocking of Tbk1 activity by a chemical inhibitor.