An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and...

Area of Science:

• Ophthalmology
• Molecular Biology
• Biotechnology

Background:

• Wet age-related macular degeneration (AMD) causes irreversible vision loss via choroidal neovascularization (CNV) and fibrosis.
• Current anti-vascular endothelial growth factor A (anti-VEGF) therapies are limited by patient resistance and drug resistance.
• Novel therapeutic strategies are needed for refractory wet AMD.

Purpose of the Study:

• Identify and characterize a DNA aptamer targeting platelet-derived growth factor-C (PDGF-C).
• Evaluate the therapeutic potential of this PDGF-C aptamer in suppressing CNV and fibrosis.
• Assess efficacy in an anti-VEGF-refractory setting.

Main Methods:

• Systematic evolution of ligands by exponential enrichment (SELEX) to identify a PDGF-C aptamer (α-PC aptamer).
• Surface plasmon resonance to assess binding and inhibition of PDGF-C/PDGFRα interaction.
• In vitro assays on fibroblasts and HUVSMCs to evaluate signaling pathways and cell behavior.
• In vivo studies in a laser-induced CNV mouse model, including anti-VEGF refractory mice.

Main Results:

• The α-PC aptamer specifically bound PDGF-C and blocked its interaction with PDGFRα.
• The aptamer inhibited PDGF-C-induced proliferation, migration, and downstream signaling (PDGFRα, Akt, ERK).
• In vivo, the α-PC aptamer significantly reduced CNV and fibrosis, maintaining efficacy in anti-VEGF refractory mice.

Conclusions:

• The PDGF-C targeting DNA aptamer is a potent inhibitor of CNV and fibrosis.
• This aptamer demonstrates therapeutic potential for wet AMD, particularly in anti-VEGF refractory cases.
• Further development of this aptamer could offer a new treatment option for neovascular diseases.