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Updated: May 17, 2026
The Corneal Micropocket Assay: A Model of Angiogenesis in the Mouse Eye
Published on: August 16, 2014
Inhibition of choroidal and corneal pathologic neovascularization by Plgf1-de gene transfer
Valeria Tarallo1, Sasha Bogdanovich, Yoshio Hirano
1Angiogenesis Lab, Institute of Genetics and Biophysics, CNR, Naples, Italy.
Purpose:
Ocular neovascularization (NV), the primary cause of blindness, typically is treated via inhibition of VEGF-A activity. However, besides VEGF-A, other proteins of the same family, including VEGF-B and placental growth factor (PlGF, all together VEGFs), have a crucial role in the angiogenesis process. PlGF and VEGF, which form heterodimers if co-expressed, both are required for pathologic angiogenesis. We generated a PlGF1 variant, named PlGF1-DE, which is unable to bind and activate VEGFR-1, but retains the ability to form heterodimer. PlGF1-DE acts as dominant negative of VEGF-A and PlGF1wt through heterodimerization mechanism. The purpose of our study was to explore the therapeutic potential of Plgf1-de gene in choroid and cornea NV context.
Methods:
In the model of laser-induced choroidal neovascularization (CNV), Plgf1-de gene, and as control Plgf1wt, LacZ, or gfp genes, were delivered using adeno-associated virus (AAV) vector by subretinal injection 14 days before the injury. After 7 days CNV volume was assessed. Corneal NV was induced by scrape or suture procedures. Expression vectors for PlGF1wt or PlGF1-DE, and as control the empty vector pCDNA3, were injected in the mouse cornea after the vascularization insults. NV was evaluated with CD31 and LYVE-1 immunostaining.
Results:
The expression of Plgf1-de induced significant inhibition of choroidal and corneal NV by reducing VEGF-A homodimer production. Conversely, the delivery of Plgf1wt, despite induced similar reduction of VEGF-A production, did not affect NV.
Conclusions:
Plgf1-de gene is a new therapeutic tool for the inhibition of VEGFs driven ocular NV.
Insights
The PlGF1-DE gene effectively inhibits ocular neovascularization (NV) by blocking VEGF-A activity. This novel gene therapy shows promise for treating conditions causing blindness like choroidal and corneal NV.
Area of Science:
- Ophthalmology
- Molecular Biology
- Gene Therapy
Background:
- Ocular neovascularization (NV) is a leading cause of blindness.
- Current treatments target VEGF-A, but other VEGF family members like VEGF-B and placental growth factor (PlGF) also contribute to angiogenesis.
- Pathologic angiogenesis requires both PlGF and VEGF, which can form heterodimers.
Purpose of the Study:
- To investigate the therapeutic potential of the PlGF1-DE gene in treating choroidal and corneal NV.
- PlGF1-DE is a modified PlGF1 variant designed to act as a dominant-negative inhibitor of VEGF-A and PlGF1 by forming heterodimers without activating VEGFR-1.
Main Methods:
- Adeno-associated virus (AAV) vectors carrying PlGF1-DE, PlGF1wt, LacZ, or GFP genes were delivered via subretinal injection in a laser-induced choroidal neovascularization (CNV) mouse model.
- Corneal NV was induced by scrape or suture, followed by injection of expression vectors for PlGF1wt, PlGF1-DE, or an empty vector.
- Neovascularization was assessed using CD31 and LYVE-1 immunostaining.
Main Results:
- Expression of PlGF1-DE significantly inhibited both choroidal and corneal NV.
- This inhibition was achieved by reducing VEGF-A homodimer production.
- PlGF1wt delivery, while reducing VEGF-A production, did not impact NV, highlighting the specific mechanism of PlGF1-DE.
Conclusions:
- The PlGF1-DE gene represents a novel therapeutic strategy for inhibiting VEGF-driven ocular neovascularization.
- This gene therapy holds potential for treating blinding conditions associated with NV.
