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Related Experiment Video

Updated: Jan 16, 2026

Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
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Melatonin Alleviates Retina Angiogenesis by Targeting Fibronectin and the VEGF Pathway.

Fang Chen1,2,3, Xi Yang4,5, Yiwei Yin6

  • 1Department of Ophthalmology, Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|September 30, 2025
PubMed
Summary

Melatonin effectively targets fibronectin (FN1) and vascular endothelial growth factor (VEGF) signaling, offering a novel therapeutic approach for retinal angiogenesis. This computer-driven discovery shows promise for treating vision-impairing diseases like diabetic retinopathy.

Keywords:
VEGF signalingangiogenesisdrug screenendothelial dysfunctionfibrosismelatonin

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Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Computational Biology

Background:

  • Diabetic retinopathy (DR) and retinopathy of prematurity (ROP) are leading causes of vision loss.
  • Pathological angiogenesis driven by vascular endothelial growth factor (VEGF) is a key factor in these conditions.
  • Understanding retinal angiogenesis's molecular mechanisms is crucial for developing new therapies.

Purpose of the Study:

  • To identify novel therapeutic targets for retinal angiogenesis.
  • To investigate the role of fibronectin (FN1) in retinal angiogenesis.
  • To explore the potential of computer-driven drug discovery for identifying inhibitors of retinal angiogenesis.

Main Methods:

  • RNA sequencing (RNA-seq) was used to analyze gene expression in an oxygen-induced retinopathy (OIR) model.
  • A deep learning model (BioNet) screened FDA-approved drugs for potential fibronectin (FN1) inhibitors.
  • In vitro and in vivo experiments validated the efficacy of melatonin in inhibiting angiogenesis.

Main Results:

  • Fibronectin (FN1) was significantly upregulated during retinal angiogenesis in the OIR model.
  • BioNet identified melatonin as a potential inhibitor of FN1.
  • Melatonin reduced FN1 expression, inhibited VEGF-induced angiogenesis, and decreased VEGFR2 phosphorylation.
  • In vivo, melatonin suppressed preretinal tufts, FN1 expression, and VEGFR2 activation in the OIR model.

Conclusions:

  • Fibronectin (FN1) plays a significant role in retinal angiogenesis.
  • Computer-driven drug discovery, exemplified by BioNet, can effectively identify novel therapeutic agents.
  • Melatonin demonstrates potential as a therapeutic agent for retinal angiogenesis by targeting both FN1 and VEGF signaling pathways.