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Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma
Chiasseu M, Cueva Vargas JL, Destroismaisons L, Vande Velde C, Leclerc N, Di Polo A.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016-05-01
Topic: Brain proteins, microglia and lab models
Unlabelled Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by the selective death of retinal ganglion cells (RGCs). Ocular hypertension is the most significant known risk factor for developing the disease, but the mechanism by which elevated pressure damages RGCs is currently unknown. The axonal-enriched microtubule-associated protein tau is a key mediator of neurotoxicity in Alzheimer's disease and other tauopathies. Using a well characterized in vivo rat glaucoma model, we show an age-related increase in endogenous retinal tau that was markedly exacerbated by ocular hypertension. Early alterations in tau phosphorylation, characterized by epitope-dependent hyperphosphorylation and hypophosphorylation, correlated with the appearance of tau oligomers in glaucomatous retinas. Our data demonstrate the mislocalization of tau in the somatodendritic compartment of RGCs subjected to high intraocular pressure. In contrast, tau was depleted from RGC axons in the optic nerve of glaucomatous eyes. Importantly, intraocular administration of short interfering RNA against tau effectively reduced retinal tau accumulation and promoted robust survival of RGC somas and axons, supporting a critical role for tau alterations in ocular hypertension-induced neuronal damage. Our study reveals that glaucoma displays signature pathological features of tauopathies, including tau accumulation, altered phosphorylation, and missorting; and identifies tau as a novel target to counter RGC neurodegeneration in glaucoma and prevalent optic neuropathies. Significance statement In this study, we investigated the role of tau in retinal ganglion cell (RGC) damage in glaucoma. We demonstrate that high intraocular pressure leads to a rapid increase in endogenous retinal tau with altered phosphorylation profile and the formation of tau oligomers. Tau accumulation was primarily observed in RGC dendrites, while tau in RGC axons within the optic nerve was depleted. Attenuation of endogenous retinal tau using a targeted siRNA led to striking protection of RGC somas and axons from hypertension-induced damage. Our study identifies novel and substantial alterations of endogenous tau protein in glaucoma, including abnormal subcellular distribution, an altered phosphorylation profile, and neurotoxicity.
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APA 7th
Chiasseu, M., Cueva Vargas, J. L., Destroismaisons, L., Vande Velde, C., Leclerc, N., & Di Polo, A. (2016). Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.3986-15.2016
Vancouver
Chiasseu M, Cueva Vargas JL, Destroismaisons L, Vande Velde C, Leclerc N, Di Polo A. Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2016. doi:10.1523/jneurosci.3986-15.2016. PMID: 27225768.
BibTeX
@article{chiasseu2016-27225768,
author = {Chiasseu, M. and Cueva Vargas, J. L. and Destroismaisons, L. and Vande Velde, C. and Leclerc, N. and Di Polo, A.},
title = {{Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2016},
doi = {10.1523/jneurosci.3986-15.2016},
pmid = {27225768},
url = {https://doi.org/10.1523/jneurosci.3986-15.2016}
}
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Key findings
- Ocular hypertension is the most significant known risk factor for developing the disease, but the mechanism by which elevated pressure damages RGCs is currently unknown.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27225768) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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