overeed mutant optineurin e50k induces retinal

Distribution and localization of abnormally

The objectives of this study were to investigate the distributions of abnormally eed optineurin (OPTN) proteins in retinal ganglion cells (RGC5s) of transgenic rats and their effects on subcellular morphological structures. Green fluorescent protein labeled EGFP wild-type (OPTN(WT)), E50K mutant type (OPTN(E50K)), and OPTN siRNA (si-OPTN) eukaryotic eion plasmids were constructed A Glaucoma-Associated Mutant of Optineurin Selectively the E50K mutant abolished ROS production and inhibited cell death. CONCLUSIONS. The E50K mutation of optineurin acquired the ability to induce cell death selectively in retinal ganglion cells. This cell death was mediated by oxidative stress. The present ndings raise the possibility of antioxidant use for delaying or controlling some forms of glaucoma. (Invest Ophthalmol Vis Sci. 2007;48:16071614)

A glaucoma-associated mutant of optineurin selectively

Eion of optineurin and its mutants was monitored by immunofluorescence staining of cells and by Western blotting. RESULTS:The E50K mutant of optineurin selectively induced the death of retinal ganglion cells but not of the other cell lines tested. Although the eion of optineurin and E50K mutant suppressed cell death induced by tumor necrosis factor-alpha in HeLa cells, they potentiated this cell death in retinal CiteSeerX A Glaucoma-Associated Mutant of Optineurin CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda):PURPOSE. Mutations in the coding region of the OPTN gene are associated with certain glaucomas. Although the function of the optineurin protein is yet to be elucidated, the most common mutation, E50K, is associated with a severe phenotype. This study explores some functional features of optineurin and its mutants. CiteSeerX E50K-OPTN-Induced Retinal Cell Death Involves A glaucoma-causing mutant of optineurin, E50K, induces death selectively in retinal cells. This mutant induces defective endocytic recycling of transferrin receptor by causing inactivation of Rab8 mediated by the GTPase-activating protein, TBC1D17.

Frontiers Altered Functions and Interactions of Glaucoma

The E50K-induced death of retinal cells can be partly reversed by knockdown of TBC1D17 and also by co-eion of TFRC. These observations suggest that TBC1D17 mediated impairment of TFRC recycling contributes to E50K-OPTN-induced apoptosis of retinal cells . The E50K mutant has lost the ability to interact with activated Rab8. Mitochondrial pathogenic mechanism and degradation in Sep 22, 2016 · A glaucoma-associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants. Investigative Ophthalmology & Visual Science 48 , 16071614 (2007). Overeion of optineurin E50K disrupts Rab8 Remarkably, we found significant phenotypical changes in five independent transgenic mouse lines eing the E50K mutant (Fig. 2 A). The retinal thickness of E50K mice was significantly reduced compared with Wt mice at 16 months of age (*P < 0.05) (Fig. 2 B), but a reduction of the retinal thickness was observed as early as 12 months of age

Significance of optineurin mutations in glaucoma and other

In this manuscript, we focus on the OPTN E50K mutation, the most common mutation for NTG, to describe the molecular mechanism of NTG by eing a mutant Optn gene in cells and genetically modified mice. Patient iPS cells were developed and differentiated into neural cells to observe abnormal behavior and the impact of the E50K mutation.The E50K optineurin mutation impacts autophagy-mediated The glaucoma-associated E50K mutation in optineurin (OPTN) is known to affect autophagy and cause the apoptosis of retinal ganglion cells (RGCs), but the pathogenic mechanism remains unclear. In this study, we investigated whether the OPTN (E50K) mutation caused TDP-43 aggregation by disrupting autophagy in vivo and in vitro.