Evidence map›Paper›PMID 40976555›Full record

ArticleJournal of advanced research2026

Epac1 deletion attenuates Müller glial pathological activation and mitigates retinal neurodegeneration in ischemia-induced retinopathy.

Shuizhen Shi, Fan Xia, Zhongqiao Lu, Erick Palacios, Fang Mei, Massoud Motamedi, Xiaodong Cheng, Hua Liu, Wenbo Zhang

Abstract read
In one paragraph

Article in Journal of advanced research, 2026. 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. ScRNA-seq Data Reveal Gene Upregulation and Downregulation in Oxygen-Induced Retinopathy.Medical science monitor : international medical journal of experimental and clinical research · 2026
    Article
  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

9 authors.

Shuizhen ShiDepartment of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Fan XiaDepartment of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Zhongqiao LuDepartment of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Erick PalaciosDepartment of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Fang MeiDepartment of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX, USA.
Massoud MotamediDepartment of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Xiaodong ChengDepartment of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX, USA; Texas Therapeutics Institute, University of Texas Health Science Center, Houston, TX, USA.
Hua LiuDepartment of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: hualiu@utmb.edu.
Wenbo ZhangDepartment of Ophthalmology & 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.

Funding

Mechanisms of Retinal Neuronal InjuryR01EY022694 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI ZHANG, WENBO · 2012 to 2021
$3.8M
Pathogenic Role of EPAC1 Signaling in Retinopathy of PrematurityR01EY026629 · NEI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI ZHANG, WENBO · 2017 to 2021
$2.6M
Epac1 as a novel therapeutic target for diabetic retinopathyR01EY033319 · NEI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI XIAODONG CHENG, Hua Liu · 2022 to 2026
$2.6M
NEI NIH HHS R01 EY022694NEI NIH HHS R01 EY026629NEI NIH HHS R01 EY033319
6 · The paper itself

Abstract

introductionIschemia-induced retinopathies, such as retinopathy of prematurity and proliferative diabetic retinopathy, are major causes of vision loss. Both pathological neovascularization and neuronal damage contribute to vision impairment in these conditions, yet current therapies primarily target neovascularization and may further compromise neuronal health.

objectivesCyclic AMP (cAMP) is a widely recognized second messenger regulating diverse physiological and pathological processes. Exchange protein directly activated by cAMP (Epac) is a recently identified effector of cAMP signaling. This study aimed to investigate the role of Epac1 in ischemia-induced retinopathy and elucidate its underlying mechanisms using a mouse model of oxygen-induced retinopathy (OIR).

methodsA mouse OIR model was established by exposing pups to 70% oxygen from postnatal day 7 (P7) to P12. Retinal structure and neuronal survival were assessed by H&E staining, TUNEL assay and immunostaining. Single-cell RNA sequencing (scRNA-seq), immunostaining, qPCR, Western blot, and proximity ligation assay were used to investigate cellular and molecular mechanisms by which Epac1 contributes to retinal pathology in OIR.

resultsGenetic deletion of Epac1 significantly protected against retinal neuronal loss and attenuated Müller glial activation in addition to reducing pathological neovascularization and promoting vascular repair. scRNA-seq revealed substantial transcriptomic alterations in Müller cells during OIR, including the emergence of reactive subclusters with distinct pathological roles, which were mitigated by Epac1 deletion. At the molecular level, Epac1 deletion restored ischemia-reduced VEGFR2 level in Müller cells during OIR, while Epac activation promoted VEGFR2 internalization and impaired VEGF signaling and its neuroprotective effects in primary Müller cells.

conclusionThese findings reveal a novel role for Epac1 in promoting retinal neurodegeneration in a mouse model of OIR through modulation of VEGF signaling in Müller cells. Targeting Epac1 may thus provide therapeutic benefit by preserving neuronal integrity in addition to its effects on vascular pathology.

Indexed as

Ependymoglial CellsGuanine Nucleotide Exchange FactorsIschemiaRetinal DegenerationAnimalsCyclic AMPDisease Models, AnimalGene DeletionMiceMice, Inbred C57BLMice, KnockoutRetinaSignal TransductionVascular Endothelial Growth Factor ACyclic AMPGuanine Nucleotide Exchange FactorsRapgef3 protein, mouseVascular Endothelial Growth Factor AEpac1Müller cellsNeurodegenerationOIRVasculopathyVEGFR2

Identifiers

PMID40976555
PMCPMC13227300

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.