Evidence map›Paper›PMID 38108689›Full record

ArticleInvestigative ophthalmology & visual science2023

Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis.

Jason Y Zhang, Jason Xiao, Bingqing Xie, Hugo Barba, Michael Boachie-Mensah, Rohan N Shah, Urooba Nadeem, Melanie Spedale, Nicholas Dylla, Huaiying Lin and 6 more

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Short-Chain Fatty Acids and the Gut-Retina Connection: A Systematic Review.International journal of molecular sciences · 2025
    Pooled it
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  20. The Effect of Metformin on Radiation-Induced Lung Fibrosis in Mice.Dose-response : a publication of International Hormesis Society
    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

16 authors at 1 institution in 1 country.

Jason Y ZhangPritzker School of Medicine, University of Chicago, Chicago, Illinois, United States.
Jason XiaoPritzker School of Medicine, University of Chicago, Chicago, Illinois, United States.
Bingqing XieDepartment of Medicine, University of Chicago, Chicago, Illinois, United States.
Hugo BarbaDepartment of Ophthalmology and Visual Science, University of Chicago, Chicago, Illinois, United States.
Michael Boachie-MensahPritzker School of Medicine, University of Chicago, Chicago, Illinois, United States.
Rohan N ShahPritzker School of Medicine, University of Chicago, Chicago, Illinois, United States.
Urooba NadeemDepartment of Pathology, University of Chicago, Chicago, Illinois, United States.
Melanie SpedaleAnimal Resources Center, University of Chicago, University of Chicago, Chicago, Illinois, United States.
Nicholas DyllaDuchossois Family Institute, University of Chicago, Chicago, Illinois, United States.
Huaiying LinDuchossois Family Institute, University of Chicago, Chicago, Illinois, United States.
Ashley M SidebottomDuchossois Family Institute, University of Chicago, Chicago, Illinois, United States.
Mark D'SouzaDuchossois Family Institute, University of Chicago, Chicago, Illinois, United States.
Betty TheriaultAnimal Resources Center, University of Chicago, University of Chicago, Chicago, Illinois, United States.
Dinanath SulakheDuchossois Family Institute, University of Chicago, Chicago, Illinois, United States.
Eugene B ChangDepartment of Medicine, University of Chicago, Chicago, Illinois, United States.
Dimitra SkondraDepartment of Ophthalmology and Visual Science, University of Chicago, Chicago, Illinois, United States.
University of Chicago · US

Funding

ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI CHANG, EUGENE B · 1990 to 2025
$29.8M
Probing short and long term consequences of Small and Large Bowel Microbiota Transplants on Host Physiology: Implications for the development of future live biotherapeuticsR01DK138072 · NIDDK · UNIVERSITY OF CHICAGO · PI EUGENE B CHANG, Kristina Brooke Martinez-Guryn · 2024 to 2026
$2.1M
NIDDK NIH HHS P30 DK042086NIDDK NIH HHS R01 DK138072
6 · The paper itself

Abstract

Purpose: Emerging data indicate that metformin may prevent the development of age-related macular degeneration (AMD). Whereas the underlying mechanisms of metformin's anti-aging properties remain undetermined, one proposed avenue is the gut microbiome. Using the laser-induced choroidal neovascularization (CNV) model, we investigate the effects of oral metformin on CNV, retinal pigment epithelium (RPE)/choroid transcriptome, and gut microbiota. Methods: Specific pathogen free (SPF) male mice were treated via daily oral gavage of metformin 300 mg/kg or vehicle. Male mice were selected to minimize sex-specific differences to laser induction and response to metformin. Laser-induced CNV size and macrophage/microglial infiltration were assessed by isolectin and Iba1 immunostaining. High-throughput RNA-seq of the RPE/choroid was performed using Illumina. Fecal pellets were analyzed for gut microbiota composition/pathways with 16S rRNA sequencing/shotgun metagenomics, as well as microbial-derived metabolites, including small-chain fatty acids and bile acids. Investigation was repeated in metformin-treated germ-free (GF) mice and antibiotic-treated/GF mice receiving fecal microbiota transplantation (FMT) from metformin-treated SPF mice. Results: Metformin treatment reduced CNV size (P < 0.01) and decreased Iba1+ macrophage/microglial infiltration (P < 0.005). One hundred forty-five differentially expressed genes were identified in the metformin-treated group (P < 0.05) with a downregulation in pro-angiogenic genes Tie1, Pgf, and Gata2. Furthermore, metformin altered the gut microbiome in favor of Bifidobacterium and Akkermansia, with a significant increase in fecal levels of butyrate, succinate, and cholic acid. Metformin did not suppress CNV in GF mice but colonization of microbiome-depleted mice with metformin-derived FMT suppressed CNV. Conclusions: These data suggest that oral metformin suppresses CNV, the hallmark lesion of advanced neovascular AMD, via gut microbiome modulation.

Indexed as

Choroidal NeovascularizationWet Macular DegenerationAngiogenesis InhibitorsAnimalsFemaleMaleMiceRetinaRNA, Ribosomal, 16SVascular Endothelial Growth Factor AVisual AcuityAngiogenesis InhibitorsRNA, Ribosomal, 16SVascular Endothelial Growth Factor A

Identifiers

PMID38108689
PMCPMC10732090
OpenAlexW4389900306

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.