Retinal tau pathology in human glaucomas

Gupta, Neeru; Fong, Jessica; Ang, Lee Cyn; Yücel, Yeni H.

doi:10.3129/i07-185

Cited by 117 publications

(108 citation statements)

References 36 publications

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“…In agreement with the epidemiological data, recent studies showed the presence of altered biomarkers of AD, such as amyloid-β, tau, and phosphorylated tau in animals with experimental glaucoma or in affected patients, supporting the hypothesis of a common pathogenesis between the diseases (Guo et al, 2007;Gupta et al, 2008;Inoue et al, 2013;Nucci et al, 2011Nucci et al, , 2015. Moreover, Wostyn et al (2008) hypothesized that the cerebrospinal fluid pressure (CSFP) may be responsible for the greater risk of glaucoma reported in patients with AD.…”

Section: Glaucoma and Neurodegenerative Diseasessupporting

confidence: 67%

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Nucci

Russo

Martucci

et al. 2016

European Journal of Pharmacology

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a b s t r a c tGlaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a number of evidences endorse the hypothesis that glaucoma is a neuro-degenerative disorder of the central nervous system and suggest a possible connection between glaucomatous damage and cerebrovascular alterations. The mechanisms underlying RGC loss are not yet fully known but alterations of the autophagy machinery have been recently proposed as a potential contributing factor as for Alzheimer's disease.Here we review the current literature on new strategies for neuroprotection in glaucoma, focusing on pharmacologic strategies to minimize RGC damage.

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Section: Glaucoma and Neurodegenerative Diseasessupporting

confidence: 67%

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Nucci

Russo

Martucci

et al. 2016

European Journal of Pharmacology

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“…12,26 Furthermore, there is emerging evidence that abnormal hyperphosphorylation of the microtubule-associated tau protein, a crucial injury marker of neuronal integrity and axonal transport in neurodegenerative diseases such as AD, was found in the retina of human glaucoma patients with elevated IOP. 27 The presence of neurotoxic Aβ and hyperphosphorylated tau, major hallmarks of AD, in experimental rat and human retinas with elevated IOP, respectively, underscores the similarities between these two agerelated neurodegenerative diseases at the molecular level. In addition to elevated IOP, decreased cerebrospinal fluid pressure, observed in a substantial proportion of patients with AD, 28 results in an abnormal high trans-lamina a The crude OR was calculated by a conditional logistic regression which was conditioned on age and the year of the index date.…”

Section: Discussionmentioning

confidence: 97%

Dementia is associated with open-angle glaucoma: a population-based study

Chung

Chen

et al. 2015

Eye

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Purpose Previous epidemiologic studies that focused on the association between openangle glaucoma (OAG) and dementia showed inconsistent results. In the present study, we explored the association between OAG and dementia in an ethnic Chinese (ie, Taiwanese) population using a population-based data set. Methods We retrieved data on study subjects for this case-control study from the Longitudinal Health Insurance Database 2000. We identified 7770 patients who had a diagnosis of dementia as cases, and 7770 subjects matched in terms of sex and age, which were randomly extracted as controls. A conditional logistic regression conditioned on age group, sex, and index year was used to assess the association of dementia with previously diagnosed OAG among the sampled patients. Results Of 15 540 patients, 1.70% had prior OAG, including 2.02% of the dementia group and 1.38% of the controls. After adjusting for patient socioeconomic characteristics and comorbid medical disorders, dementia patients were more likely to have had prior OAG than controls (odds ratio (OR): 1.44; 95% confidence interval (CI): 1.12-1.85; Po0.01). In addition, female dementia patients were more likely to have had prior OAG than controls (OR: 1.93; 95% CI: 1.35-2.77; Po0.001), whereas no statistical difference in prior OAG between male dementia patients and controls was found. Conclusions Female dementia patients were associated with a higher proportion of prior OAG than were the controls.

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“…The observation of abnormal TAU phosphorylation in a model lacking a thioredoxin family member strengthens the role of thioredoxin signaling in controlling the redox status of TAU and oxidative stress in neuronal tissues. Indeed this is the second time that an abnormal phosphorylation of TAU has been observed in the retina: hyperphosphorylated TAU was recently detected in the retina of patients suffering from glaucoma (48). The hyperphosphorylation of TAU in the retina of the Nxnl1 Ϫ/Ϫ mouse (Fig.…”

Section: Discussionmentioning

confidence: 99%

The Thioredoxin-like Protein Rod-derived Cone Viability Factor (RdCVFL) Interacts with TAU and Inhibits Its Phosphorylation in the Retina

Fridlich

Delalande

Jaillard

et al. 2009

Molecular & Cellular Proteomics

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Rod-derived cone viability factor (RdCVF) is produced by the Nxnl1 gene that codes for a second polypeptide, RdCVFL, by alternative splicing. Although the role of RdCVF in promoting cone survival has been described, the implication of RdCVFL, a putative thioredoxin enzyme, in the protection of photoreceptors is presently unknown. Using a proteomics approach we identified 90 proteins interacting with RdCVFL including the microtubule-binding protein TAU. We demonstrate that the level of phosphorylation of TAU is increased in the retina of the Nxnl1 ؊/؊ mice as it is hyperphosphorylated in the brain of patients suffering from Alzheimer disease, presumably in some cases through oxidative stress. Using a cell-based assay, we show that RdCVFL inhibits TAU phosphorylation. In vitro, RdCVFL protects TAU from oxidative damage. Photooxidative stress is implicated in retinal degeneration, particularly in retinitis pigmentosa, where it is considered to be a contributor to secondary cone death. The functional interaction between RdCVFL and TAU described here is the first characterization of the RdCVFL signaling pathway involved in neuronal cell death mediated by oxidative stress.

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Retinal tau pathology in human glaucomas

Cited by 117 publications

References 36 publications

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Dementia is associated with open-angle glaucoma: a population-based study

The Thioredoxin-like Protein Rod-derived Cone Viability Factor (RdCVFL) Interacts with TAU and Inhibits Its Phosphorylation in the Retina

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