Therapeutic Exosomes Carrying VEGFA siRNA Inhibit Pathological Corneal Angiogenesis via PI3K-Akt-Caspase-3 Signaling

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Gene Therapy

Background:

• Pathological neovascularization is a key factor in corneal vision loss.
• Vascular endothelial growth factor A (VEGFA) drives pathological neovascularization.
• Exosomes offer a promising platform for targeted gene delivery due to their stability and low immunogenicity.

Purpose of the Study:

• To investigate the efficacy of mesenchymal stem cell (MSC)-derived exosomes loaded with VEGFA siRNA in suppressing corneal neovascularization (CNV).
• To examine the underlying molecular mechanisms, including the PI3K-Akt-Caspase-3 signaling pathway.
• To evaluate the safety profile of this exosome-based therapy.

Main Methods:

• Exosomes were purified from MSCs and characterized.
• In vitro studies assessed exosome uptake, VEGFA inhibition, cell viability, and apoptosis.
• In vivo studies utilized a mouse CNV model to evaluate therapeutic effects and systemic safety.

Main Results:

• Exosomes effectively delivered VEGFA siRNA, reducing VEGFA expression and inducing apoptosis in vitro.
• In vivo, exosomes significantly inhibited CNV, reduced CD31 and VEGFA levels, and modulated the PI3K-Akt-Caspase-3 pathway.
• Histological analysis showed reduced neovascularization and inflammation, with no observed systemic toxicity.

Conclusions:

• VEGFA siRNA-loaded exosomes are effective in reducing pathological CNV through targeted gene inhibition and apoptosis induction.
• The therapy modulates the PI3K-Akt pathway, leading to caspase-3-mediated apoptosis.
• These exosomes represent a promising local gene therapy for ocular neovascular diseases.