Evidence map›Paper›PMID 38659223›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.

Fan Xia, Shuizhen Shi, Erick Palacios, Wei Liu, Seth E Buscho, Joseph Li, Shixia Huang, Gianmarco Vizzeri, Xiaocheng Charlie Dong, Massoud Motamedi and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 17 citations in OpenAlex.

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  9. Neuroprotection beyond intraocular pressure: game changer or quiet addiction.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Fan XiaDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Shuizhen ShiDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Erick PalaciosDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Wei LiuDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Seth E BuschoDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Joseph LiDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Shixia HuangAdvanced Technology Cores, Department of Molecular and Cellular Biology, Department of Education, Innovation and Technology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Gianmarco VizzeriDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Xiaocheng Charlie DongDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Massoud MotamediDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Wenbo ZhangDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Neurobiology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: we2zhang@utmb.edu.
Hua LiuDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: hualiu@utmb.edu.
The University of Texas Medical Branch at Galveston · USChildren's Cancer Center · USIndiana University School of Medicine

Funding

Mechanisms of Retinal Neuronal InjuryR01EY022694 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI ZHANG, WENBO · 2012 to 2021
$3.8M
Neuroprotective Role of Sirt6 in GlaucomaR01EY031054 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI LIU, HUA · 2020 to 2024
$2.8M
Pathogenic Role of EPAC1 Signaling in Retinopathy of PrematurityR01EY026629 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI ZHANG, WENBO · 2017 to 2021
$2.6M
CXCR3-Mediated Cell-Cell Communication in GlaucomaR01EY034376 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Gracie Vargas, Fan Xia · 2022 to 2026
$2.2M
Epigenetic regulation in liver fibrosisR01DK121925 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2020 to 2023
$1.8M
Role of SIRT6 in the pancreatic beta cell agingR21AG072288 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI DONG, X. CHARLIE · 2022 to 2023
$436k
NEI NIH HHS R01 EY022694NEI NIH HHS R01 EY026629NEI NIH HHS R01 EY031054NEI NIH HHS R01 EY034376NIA NIH HHS R21 AG072288NIDDK NIH HHS R01 DK121925
6 · The paper itself

Abstract

Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights into the complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during aging, despite normal intraocular pressure (IOP), resembling a phenotype of normal-tension glaucoma. These detrimental effects were potentially mediated by accelerated RGC senescence through Caveolin-1 upregulation and by the induction of mitochondrial dysfunction. In mouse models of high-tension glaucoma, Sirt6 level was decreased after IOP elevation. Genetic overexpression of Sirt6 globally or specifically in RGCs significantly attenuated high tension-induced degeneration of RGCs and their axons, whereas partial or RGC-specific Sirt6 deletion accelerated RGC loss. Importantly, therapeutically targeting Sirt6 with pharmacological activator or AAV2-mediated gene delivery ameliorated high IOP-induced RGC degeneration. Together, our studies reveal a critical role of Sirt6 in preventing RGC and optic nerve degeneration during aging and glaucoma, setting the stage for further exploration of Sirt6 activation as a potential therapy for glaucoma.

Indexed as

AgingDisease Models, AnimalGlaucomaOptic NerveRetinal Ganglion CellsSirtuinsAnimalsAxonsHumansIntraocular PressureMiceMice, KnockoutNerve DegenerationSirt6 protein, mouseSirtuinsAAV2agingglaucomaneurodegenerationoptic nerveretinal ganglion cellsSirt6Sirt6 activator

Identifiers

PMID38659223
PMCPMC11184404
OpenAlexW4395080636

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.