Disease relevance of Optn

• Mutations in the optineurin (optic neuropathy inducing) protein were found associated with an adult form of glaucoma [1].
• In this study, to elucidate the role of Angptl3 in atherogenesis, we investigated the effects of hypl mutation against hyperlipidemia and atherosclerosis in apolipoprotein E knockout (apoEKO) mice [2].

High impact information on Optn

• This T-lymphocyte population recognizes two related peptides (NRP and NRP-A7) in the context of H-2Kd class I molecules of the major histocompatibility complex (MHC) [3].
• During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system [4].
• This translocation is dependent on the GTPase activity of Rab8, an interactor of optineurin [1].
• The correlation between optineurin function and cell survival will be key to begin to understand retinal ganglion cell biology and signaling and to design general "survival" strategies to treat a disease of such a complex etiology as glaucoma [1].
• Furthermore, we demonstrate that the overexpression of optineurin protects cells from H2O2-induced cell death and blocks cytochrome c release from the mitochondria [1].

Biological context of Optn

• We mapped Optn to chromosome 2, within a region that is syntenic to human 10p14 [5].
• Optn has 13 coding exons and its exon-intron boundaries are evolutionarily conserved with human [5].
• The goal of the present study was to study the molecular properties of optineurin and its capabilities to prevent apoptosis in vivo in the eyes of transgenic mice [6].

Anatomical context of Optn

• Optn colocalizes with vesicular structures near the nucleus and is expressed in anterior segment, retina, and optic nerve blood vessels [5].
• A mutated form of optineurin, E50K, identified in normal tension glaucoma patients loses its ability to translocate to the nucleus and when overexpressed compromises the mitochondrial membrane integrity resulting in cells that are less fit to survive under stress conditions [1].
• The NRP-reactive, in vivo activated CD8(+) cells arising in pancreatic islets of nonobese diabetic mice are similarly promiscuous for peptide/MHC, and paradoxically this promiscuity expands as the aviditiy of the T cell population for NRP/MHC increases with age [7].
• Neither transgenic nor endogenous optineurin was found in the aqueous humor [6].
• Immunostaining for endogenous optineurin in the anterior eye was considerably weaker than in the posterior eye and was seen in iris, ciliary epithelium, cells of corneal stroma and endothelium, and in the trabecular meshwork [6].

Other interactions of Optn

• Optineurin increases cell survival and translocates to the nucleus in a Rab8-dependent manner upon an apoptotic stimulus [1].
• To assess effects of transgenic optineurin on apoptosis, betaB1-crystallin-OPTN mice were crossbred with betaB1-crystallin-TGFbeta1 mice that undergo substantial TGF-beta1-induced apoptotic cell death in the lens [6].
• As optineurin interferes with TNF-alpha mediated cell death in vitro, an involvement of optineurin in the regulatory pathways leading to apoptosis of retinal ganglion cells has been suggested [6].

Analytical, diagnostic and therapeutic context of Optn

• Molecular cloning, genomic structure, and protein characterization of mouse optineurin [5].
• Two independent betaB1-crystallin-OPTN transgenic lines were established, in which transgenic optineurin was expressed strictly lens-specific as assessed by Northern and Western blotting, and by immunohistochemistry [6].
• The localization of transgenic optineurin was investigated by one- and two-dimensional western blot analysis and by immunohistochemistry, and compared with that of endogenous optineurin [6].

References