Variants in Optineurin Gene and Their Association with Tumor Necrosis Factor-α Polymorphisms in Japanese Patients with Glaucoma

Funayama, Tomoyo; Ishikawa, Kenzo; Ohtake, Yuichiro; Tanino, Tomihiko; Kurosaka, Daijiro; Kimura, Ikuo; Suzuki, Kotaro; Ideta, Hidenao; Nakamoto, Kenji; Yasuda, Noriko; Fujimaki, Takamitsu; Murakami, Akira; Asaoka, Ryo; Hotta, Yoshihiro; Tanihara, Hidenobu; Kanamoto, Takashi; Mishima, Hiromu K.; Fukuchi, Takeo; Abe, Haruki; Iwata, Takeshi; Shimada, Naoki; Kudoh, Jun; Shimizu, Nobuyoshi; Mashima, Yukihiko

doi:10.1167/iovs.03-1403

Cited by 92 publications

(79 citation statements)

References 42 publications

(50 reference statements)

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“…An OR of 0.96 for POAG was found in carriers of the TNF-a À308A-allele, suggesting that this polymorphism is not a risk factor for POAG. This is in contrast to the findings of Lin et al, 20 who reported a significantly increased prevalence of the TNF-a À308A-allele among 60 Chinese patients with POAG with an OR of 2.72 for POAG among carriers of the TNF-a À308A-allele. 18 Possible explanations for these conflicting results may include small sample size as well as varying genotype distributions among different populations.…”

Section: Discussioncontrasting

confidence: 99%

TNF-α promoter polymorphisms and primary open-angle glaucoma

Mossböck

Weger

Moray

et al. 2005

Eye

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Purpose Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-a (TNF-a) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-a À308G4A and À238G4A gene polymorphisms and the presence of POAG in a Caucasian population. Methods The present case-control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-a À308G4A and À238G4A polymorphisms was performed using polymerase chain reaction. Results Allelic frequencies and genotype distributions of both the TNF-a À308G4A and À238G4A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-a À308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-a À238A-allele. Conclusion Our data suggest that none of the investigated TNF-a gene polymorphisms is a major risk factor among Caucasian patients with POAG.

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Section: Discussioncontrasting

confidence: 99%

TNF-α promoter polymorphisms and primary open-angle glaucoma

Mossböck

Weger

Moray

et al. 2005

Eye

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“…Allelic frequencies and genotype distributions did not significantly differ between the 2 groups. This is in line with Funayama and associates (Funayama et al, 2004) who investigated the association between sequence variation in the Optineurin gene and the polymorphisms in the TNF-alpha promoter region, at positions -308, -857 and -863 in Japanese POAG patients. Optineurin expression is induced by tumor necrosis factor-alpha and interferes with adenoviral E3-14.7K protein which safeguards cells from the neurodegenerative effect of TNF-α.…”

Section: Discussionsupporting

confidence: 87%

The -863 TNF-α Polymorphism and Primary Open Angle Glaucoma in Egyptians

Gazzar¹,

Rahman²,

Elmohamady³

et al. 2017

American Journal of Biochemistry and Biotechnology

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Growing evidence indicates that TNF-alpha is involved in the pathogenesis of POAG in several ways, primarly by induction of retinal ganglion cells apoptosis and therefore optic nerve degeneration. TNF-alpha and POAG relationship has been studied at the genetic level with variable results in different populations. The transcription rate and the release of the TNF-alpha cytokine have been reported to be affected by polymorphisms in the promoter of the TNF-alpha gene. Polymorphisms at positions -238 and -308 are the most frequent studied. Another polymorphism, at the position -863 in the promoter region, has been less studied, but a homozygous AA allele appears protective in a Chinese population. Our aim was to assess the potential association of -863C/A TNF-alpha gene promoter polymorphisms with POAG in an Egyptian group of subjects. Genotyping of the TNF-alpha (-863) polymorphism was done for 228 POAG patients and 230 control subjects using the PCRbased, Restriction Fragment Length Polymorphism (RFLP) assay. TNFalpha (-863) A/A genotype was absent in both groups. There was no significant difference between both groups as regards to TNF-α (-863) A allele carriage (6.14 versus 10.43%; p = 0. 099)). Also the genotype TNF-α (-863) C/C and the frequency of the tumor necrosis factor-alpha (-863) C allele did not significantly differ between both groups (93.86 versus 89.57%; p = 0. 099) and 96.93 versus 94.78%; p = 0. 107) respectively. Our data indicated that the TNF-alpha (-863) a allele is not linked with primary open angle glaucoma protection among Egyptian patients.

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“…A common characteristic of all forms of glaucoma is the death of RGCs (40). Of significant interest, TNFα and TNFR1 are up-regulated in human donor eyes with glaucoma (19,41,42), TNFα levels are increased in the aqueous humor of glaucoma patients (43), and TNFα gene polymorphisms have been correlated with primary open angle glaucoma (44,45). Therefore, an important priority in future studies will be to determine if the proNGF, p75 NTR , and TNFα cascade described here contributes to retinal degeneration and optic neuropathy in preclinical models of disease and in humans.…”

Section: Resultsmentioning

confidence: 99%

ProNGF induces TNFα-dependent death of retinal ganglion cells through a p75 ^NTR non-cell-autonomous signaling pathway

Lebrun-Julien

Bertrand

Backer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

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Neurotrophin binding to the p75 neurotrophin receptor (p75 NTR ) activates neuronal apoptosis following adult central nervous system injury, but the underlying cellular mechanisms remain poorly defined. In this study, we show that the proform of nerve growth factor (proNGF) induces death of retinal ganglion cells in adult rodents via a p75 NTR -dependent signaling mechanism. Expression of p75 NTR in the adult retina is confined to Müller glial cells; therefore we tested the hypothesis that proNGF activates a non-cellautonomous signaling pathway to induce retinal ganglion cell (RGC) death. Consistent with this, we show that proNGF induced robust expression of tumor necrosis factor alpha (TNFα) in Müller cells and that genetic or biochemical ablation of TNFα blocked proNGF-induced death of retinal neurons. Mice rendered null for p75 NTR , its coreceptor sortilin, or the adaptor protein NRAGE were defective in proNGF-induced glial TNFα production and did not undergo proNGF-induced retinal ganglion cell death. We conclude that proNGF activates a non-cell-autonomous signaling pathway that causes TNFα-dependent death of retinal neurons in vivo.T he four mammalian neurotrophins comprise a family of related secreted factors that are required for differentiation, survival, development, and death of specific populations of neurons and nonneuronal cells. Neurotrophins are produced as proforms of ∼240 amino acids that are cleaved by furins and proconvertases to yield products of ∼120 amino acids. Recent studies have indicated that nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) can be secreted as proforms in the central nervous system (CNS) (1-3) and demonstrated that proneurotrophins can function as potent apoptosis-inducing ligands both in vitro and in vivo (4). However, the precise mechanisms by which proneurotrophins lead to neuronal death are poorly defined.The biological effects of neurotrophins are mediated by binding to TrkA, TrkB, and TrkC receptor tyrosine kinases and to the p75 neurotrophin receptor (p75 NTR ). Trk receptors respond preferentially to mature neurotrophins whereas proneurotrophins exert their apoptotic effect via a receptor complex that contains p75 NTR and sortilin (5). The precise signaling cascades evoked by occupancy of the p75 NTR -sortilin complex remain to be elucidated, but several lines of evidence indicate that NRIF and NRAGE adaptor proteins play key roles in death signaling cascades evoked by p75 NTR (6, 7).Previous studies have shown that neurotrophins induce cell death via p75 NTR during early retinal development (8). p75 NTR has also been implicated in light-induced photoreceptor death in adult rodents in vivo (9) and a proNGF-p75 NTR link has been proposed to facilitate apoptosis in a retinal cell line (10). Here, we investigate the role of proNGF in the adult retina and demonstrate that proNGF promotes death of retinal ganglion cells (RGCs) in vivo. Importantly, proNGF-induced RGC loss is indirect and requires the p75 NTRdependent production of tumor necrosis...

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Variants in Optineurin Gene and Their Association with Tumor Necrosis Factor-α Polymorphisms in Japanese Patients with Glaucoma

Abstract: These findings demonstrated that the OPTN gene is associated with POAG rather than NTG in the Japanese. Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-alpha genes that would increase the risk for glaucoma.

Cited by 92 publications

References 42 publications

TNF-α promoter polymorphisms and primary open-angle glaucoma

TNF-α promoter polymorphisms and primary open-angle glaucoma

The -863 TNF-α Polymorphism and Primary Open Angle Glaucoma in Egyptians

ProNGF induces TNFα-dependent death of retinal ganglion cells through a p75 ^NTR non-cell-autonomous signaling pathway

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Variants in Optineurin Gene and Their Association with Tumor Necrosis Factor-α Polymorphisms in Japanese Patients with Glaucoma

Abstract: These findings demonstrated that the OPTN gene is associated with POAG rather than NTG in the Japanese. Statistical analysis showed a possible interaction between polymorphisms in the OPTN and the TNF-alpha genes that would increase the risk for glaucoma.

Cited by 92 publications

References 42 publications

TNF-α promoter polymorphisms and primary open-angle glaucoma

TNF-α promoter polymorphisms and primary open-angle glaucoma

The -863 TNF-&alpha; Polymorphism and Primary Open Angle Glaucoma in Egyptians

ProNGF induces TNFα-dependent death of retinal ganglion cells through a p75 NTR non-cell-autonomous signaling pathway

Contact Info

Product

Resources

About

The -863 TNF-α Polymorphism and Primary Open Angle Glaucoma in Egyptians

ProNGF induces TNFα-dependent death of retinal ganglion cells through a p75 ^NTR non-cell-autonomous signaling pathway