Evidence mapPaperPMID 41285704Full record

ArticleCell death discovery2025

Metformin protects retinal ganglion cells in a preclinical model of retinal ischemia/reperfusion injury and stabilizes visual field in diabetic patients with glaucoma.

Andrea Satriano, Alessio Martucci, Annagrazia Adornetto, Elisabetta Benfatto, Gianluca Tettamanti, Daniele Bruno, Maria Tiziana Corasaniti, Giacinto Bagetta, Carlo Nucci, Rossella Russo

Abstract read
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

10 authors.

Andrea Satriano *Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, Arcavacata di Rende, Italy.
Alessio Martucci *Department of Experimental Medicine, Ophthalmology Unit, University of Rome "Tor Vergata", Rome, Italy.
Annagrazia AdornettoDepartment of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, Arcavacata di Rende, Italy.ORCID http://orcid.org/0000-0003-1869-2642
Elisabetta BenfattoDepartment of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, Arcavacata di Rende, Italy.
Gianluca TettamantiDepartment of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.ORCID http://orcid.org/0000-0002-0665-828X
Daniele BrunoDepartment of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.ORCID http://orcid.org/0000-0002-2550-3267
Maria Tiziana CorasanitiDepartment of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.ORCID http://orcid.org/0000-0001-6472-0697
Giacinto BagettaDepartment of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, Arcavacata di Rende, Italy.
Carlo NucciDepartment of Experimental Medicine, Ophthalmology Unit, University of Rome "Tor Vergata", Rome, Italy.
Rossella RussoDepartment of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, Arcavacata di Rende, Italy. rossella.russo@unical.it.ORCID http://orcid.org/0000-0001-8758-6523

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin, a first-line treatment for type 2 diabetes, has gained attention as a promising neuroprotective agent due to its pleiotropic effects - including anti-inflammatory, anti-apoptotic, and autophagy-enhancing properties. Here we provide both preclinical and clinical evidence demonstrating the neuroprotective effects of metformin in the context of retinal ganglion cell (RGC) degeneration, a hallmark of glaucoma, a leading cause of irreversible blindness for which no direct RGC-neuroprotective therapies are currently available. In a mouse model of retinal ischemia/reperfusion injury systemic administration of metformin significantly prevented RGC loss and preserved retinal structure. Enhanced phosphorylation of AMP-activated protein kinase (AMPK) was observed, along with increased autophagosome formation and upregulation of key mitophagy markers - including LC3II, optineurin, and Parkin - indicating improved mitochondrial quality control mechanisms. Proteomic analysis revealed that metformin modulated several proteins implicated in mitochondrial respiratory function, ubiquitination, and intracellular trafficking, suggesting broader effects on retinal cellular homeostasis. Complementing our preclinical observations, a retrospective clinical study in diabetic patients with glaucoma showed that individuals treated with metformin maintained stable visual field (VF) parameters over a six-month period, whereas those treated with insulin exhibited significant VF deterioration. These findings position metformin as a promising intraocular pressure (IOP)-independent neurotherapeutic for slowing or preventing glaucomatous neurodegeneration.

Identifiers

PMID41285704
PMCPMC12645046

What Socratic holds

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Registered trials

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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 Socratic graph.