Related Experiment Video

Updated: Jul 5, 2025

An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
08:10

An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy

Published on: January 25, 2019

7.8K

Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy

Xinjing Wu1, Bing Qin2, Ruiwen Cheng1

  • 1Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

International Journal of Biological Sciences
|January 22, 2024
PubMed

Insights

Gremlin1, a novel protein, drives ocular angiogenesis and fibrosis in diseases like proliferative diabetic retinopathy (PDR). Targeting Gremlin1 with antibodies shows promise for treating these vision-threatening conditions.

Area of Science:

  • Ophthalmology
  • Vascular Biology
  • Cell Biology

Background:

  • Ocular angiogenic diseases, including proliferative diabetic retinopathy (PDR), involve pathological neovascularization and fibrosis.
  • Current anti-vascular endothelial growth factor (VEGF) therapies face challenges like drug resistance and persistent retinal fibrosis.

Purpose of the Study:

  • To investigate the role of Gremlin1, a novel inducer, in ocular angiogenesis and fibrosis.
  • To explore Gremlin1's mechanism of action and its potential as a therapeutic target.

Main Methods:

  • Quantified Gremlin1 expression in vitreous fluid from PDR patients.
  • Elucidated Gremlin1's signaling pathways (EGFR/RhoA/ROCK) in endothelial-mesenchymal transition.
  • Assessed the effect of anti-Gremlin1 antibodies on ocular angiogenesis and microglia-mediated fibrosis in mouse models.

Main Results:

  • Gremlin1 expression is elevated in PDR patients' vitreous fluid.
  • Gremlin1 induces angiogenesis by promoting endothelial-mesenchymal transition via the EGFR/RhoA/ROCK pathway.
  • Gremlin1 activates microglia, contributing to profibrotic and fibrogenic activities; anti-Gremlin1 therapy reduced ocular angiogenesis and fibrosis in vivo.

Conclusions:

  • Gremlin1 is a key mediator of pathological angiogenesis and fibrosis in ocular diseases.
  • Targeting Gremlin1 presents a promising therapeutic strategy for PDR and related conditions.
Keywords:
AngiogenesisFibrosisGremlin1MicrogliaProliferative diabetic retinopathy

More Related Videos

Regenerative Therapy by Suprachoroidal Cell Autograft in Dry Age-related Macular Degeneration: Preliminary In Vivo Report10:24

Regenerative Therapy by Suprachoroidal Cell Autograft in Dry Age-related Macular Degeneration: Preliminary In Vivo Report

Published on: February 12, 2018

10.2K
Characterization of a Novel Human Organotypic Retinal Culture Technique05:51

Characterization of a Novel Human Organotypic Retinal Culture Technique

Published on: June 9, 2021

4.0K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.5K