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Topical ocular administration of the GLP-1 receptor agonist liraglutide arrests hyperphosphorylated tau-triggered diabetic retinal neurodegeneration via activation of GLP-1R/Akt/GSK3β signaling
Shu X, Zhang Y, Li M, Huang X, Yang Y, Zeng J, Zhao Y, Wang X et al.. Neuropharmacology, 2019-04-20
Topic: Brain proteins, microglia and lab models
Diabetic retinal neurodegeneration, in particular synaptic neurodegeneration of retinal ganglion cells (RGCs) occurring before RGCs apoptosis, may represent the earliest event in the pathogenesis of diabetic retinopathy (DR). Our previous study identified hyperphosphorylated-tau as a critical toxic mediator in diabetic RGCs synaptic neurodegeneration. Thus, therapeutic agents targeting to tau may appear as a promising strategy to arrest the progression of DR. The glucagon-like-peptide 1 receptor (GLP-1R) agonists, including liraglutide, can ameliorate neurodegenerative features in models of Alzheimer's disease and diabetes by decreasing tau hyperphosphorylation in the brain. Liraglutide has also been found to prevent retinal neural apoptosis/loss in diabetic mice. However, whether liraglutide can prevent diabetic synapse degeneration of RGCs, and its neuroprotective role, if any, is due to alleviating retinal tau hyperphosphorylation remain unknown. Here, using a well characterized high-fat diet (HFD)-induced diabetes mouse model, we showed that topical ocular administration of liraglutide reversed hyperphosphorylated tau-triggered RGCs synaptic degeneration in HFD-induced diabetes. The neuroprotective effect of liraglutide on diabetic retinae was abolished when GLP-1R or Akt was inhibited by topically co-administration with a GLP-1R antagonist, exendin-(9-39), or an Akt inhibitor MK2206, respectively. However, knock-down of GSK3β by intravitreal injection of si-GSK3β restored the neuroprotective effects of liraglutide abrogated by Akt inactivation. Thus, our present study demonstrated that liraglutide can arrest hyperphosphorylated tau-triggered retinal neurodegeneration via activation of GLP-1R/Akt/GSK3β signaling. Our results also propose that topical ocular application of liraglutide can be envisaged as a potentially useful strategy for the treatment of retinal tauopathy at the early onset of DR.
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APA 7th
Shu, X., Zhang, Y., Li, M., Huang, X., Yang, Y., Zeng, J., et al. (2019). Topical ocular administration of the GLP-1 receptor agonist liraglutide arrests hyperphosphorylated tau-triggered diabetic retinal neurodegeneration via activation of GLP-1R/Akt/GSK3β signaling. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2019.04.018
Vancouver
Shu X, Zhang Y, Li M, Huang X, Yang Y, Zeng J, et al. Topical ocular administration of the GLP-1 receptor agonist liraglutide arrests hyperphosphorylated tau-triggered diabetic retinal neurodegeneration via activation of GLP-1R/Akt/GSK3β signaling. Neuropharmacology. 2019. doi:10.1016/j.neuropharm.2019.04.018. PMID: 31015047.
BibTeX
@article{shu2019-31015047,
author = {Shu, X. and Zhang, Y. and Li, M. and Huang, X. and Yang, Y. and Zeng, J. and Zhao, Y. and Wang, X. and others},
title = {{Topical ocular administration of the GLP-1 receptor agonist liraglutide arrests hyperphosphorylated tau-triggered diabetic retinal neurodegeneration via activation of GLP-1R/Akt/GSK3β signaling}},
journal = {Neuropharmacology},
year = {2019},
doi = {10.1016/j.neuropharm.2019.04.018},
pmid = {31015047},
url = {https://doi.org/10.1016/j.neuropharm.2019.04.018}
}
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Key findings
- Here, using a well characterized high-fat diet (HFD)-induced diabetes mouse model, we showed that topical ocular administration of liraglutide reversed hyperphosphorylated tau-triggered RGCs synaptic degeneration in HFD-induced diabetes.
- Thus, our present study demonstrated that liraglutide can arrest hyperphosphorylated tau-triggered retinal neurodegeneration via activation of GLP-1R/Akt/GSK3β signaling.
- Our results also propose that topical ocular application of liraglutide can be envisaged as a potentially useful strategy for the treatment of retinal tauopathy at the early onset of DR.
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Study details
- Evidence strengthLow
How this study scored 38/100
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 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuropharmacology) |
| 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 | 2 / 5 | 2019 — within 10 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 31015047) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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