Distribution of Optineurin Sequence Variations in an Ethnically Diverse Population of Low-tension Glaucoma Patients From the United States

Hauser, Michael A.; Sena, Dayse F; Flor, J.D.; Walter, Jeff; Auguste, J.; LaRocque-Abramson, Karen; Graham, Felicia L.; DelBono, E.; Haines, Jonathan L.; Pericak‐Vance, Margaret A.; Allingham, R. Rand; Wiggs, Janey L.

doi:10.1097/01.ijg.0000212255.17950.42

Cited by 81 publications

(49 citation statements)

References 22 publications

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“…23 Optineurin mutations were noted to vary with ethnic background. 24,25 The Glu50Lys (E50K) mutation, found in Caucasian and Hispanic populations, 25 seems to be associated with a more progressive and severe disease in patients with normal tension glaucoma. 26 The human optineurin gene codes for a 577-amino acid protein that contains multiple coiled-coil domains and a C-terminal zinc finger.…”

mentioning

confidence: 99%

Differential Effects of Myocilin and Optineurin, Two Glaucoma Genes, on Neurite Outgrowth

Koga

Shen

Park

et al. 2010

The American Journal of Pathology

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Myocilin and optineurin are two genes linked to glaucoma , a major blinding disease characterized by progressive loss of retinal ganglion cells (RGCs) and their axons. To investigate the effects of force-expressed wild-type and mutant myocilin and optineurin on neurite outgrowth in neuronal cells , we transiently transfected cells with pEGFP-N1 (mock control) as well as myocilin and optineurin plasmids including pMYOC WT -EGFP, pMYOC P370L -EGFP, pMYOC 1-367 -EGFP, pOPTN WT -EGFP , and pOPTN E50K -EGFP. PC12 cells transfected with pEGFP-N1 produced , as anticipated, long and extensive neuritis on nerve growth factor induction. The neurite length in those cells transfected with myocilin constructs was shortened and the number of neurites was also reduced. A similar inhibitory effect on neurite outgrowth was also elicited by myocilin transfection in RGC5 cells. In contrast , neither transfection of the optineurin constructs pOPTN WT -EGFP and pOPTN E50K -EGFP nor the myocilin and optineurin small-interfering RNA treatments induced significant alterations in neurite outgrowth. Transfection with the wild-type optineurin construct , but not with that of the wild-type myocilin, increased the apoptotic activity in cells. These results demonstrated that the two glaucoma genes , myocilin and optineurin, exhibited differential effects on neurite outgrowth. They may contribute to the development of neurodegenerative glaucoma via distinct mechanisms.

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mentioning

confidence: 99%

Differential Effects of Myocilin and Optineurin, Two Glaucoma Genes, on Neurite Outgrowth

Koga

Shen

Park

et al. 2010

The American Journal of Pathology

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“…Mutations in OPTN appear to be clustered in patients with low tension glaucoma (LTG) [13]. One non-synonymous 3 mutation, a single base change gaunine (G) to adenine (A) at position 458 of exon 44, replaces the amino acid glutamic acid with a lysine.…”

Section: Single Genes and Glaucomamentioning

confidence: 99%

Pharmacogenetics - Getting Closer

MacDonald¹

2009

TOOPHTJ

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“…It is expected that certain glaucoma-predisposing genes will specifically influence ganglion cell death in the setting of elevated IOP or even normal IOP. Ganglion cell apoptosis is associated with a mutant form of optineurin (56,57), and WDR36 variants may increase the degree of ganglion cell loss (62). Gene-specific pathophysiology has not yet been established for other glaucoma-causing genes.…”

Section: Pathophysiology Associated With Current Glaucoma Genesmentioning

confidence: 99%

“…Model-dependent linkage analyses using multiplex POAG pedigrees have yielded a number of potential POAG loci (GLC1A-GLC1H and GLC1L; Table 1) but few genes. Optineurin (OPTN) at GLC1E (10p15-p14) (56), although initially described as a POAG-causative gene, is primarily responsible for rare cases of familial NTG, a type of open-angle glaucoma in which the optic nerve deteriorates despite normal IOP (57,58). Optineurin may influence ganglion cell apoptosis directly through rab8 signaling (59,60).…”

Section: Figurementioning

confidence: 99%

Glaucoma: genes, phenotypes, and new directions for therapy

Fan

Wiggs²

2010

J. Clin. Invest.

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128

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Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative. This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible.

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Distribution of Optineurin Sequence Variations in an Ethnically Diverse Population of Low-tension Glaucoma Patients From the United States

Cited by 81 publications

References 22 publications

Differential Effects of Myocilin and Optineurin, Two Glaucoma Genes, on Neurite Outgrowth

Differential Effects of Myocilin and Optineurin, Two Glaucoma Genes, on Neurite Outgrowth

Pharmacogenetics - Getting Closer

Glaucoma: genes, phenotypes, and new directions for therapy

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