Cannabidiol-Loaded Retinal Organoid-Derived Extracellular Vesicles Protect Oxidatively Stressed ARPE-19 Cells

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Nanotechnology

Background:

• Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in individuals over 50.
• Oxidative stress is a key factor in AMD pathogenesis.
• Extracellular vesicles (EVs) from retinal organoids facilitate cell communication and tissue remodeling.

Purpose of the Study:

• To encapsulate cannabidiol (CBD), a hydrophobic compound, into retinal organoid-derived EVs (CBD-EVs).
• To evaluate the therapeutic potential of CBD-EVs for treating AMD.
• To investigate the effects of CBD-EVs on oxidative stress in retinal pigment epithelial cells.

Main Methods:

• Human induced pluripotent stem cell (hiPSC)-derived retinal organoid EVs were loaded with CBD via sonication.
• Structural analysis of CBD-EVs used atomic force microscopy and nanoparticle tracking analysis.
• Cytotoxicity, reactive oxygen species (ROS), and antioxidant protein expression were assessed in ARPE-19 cells treated with CBD-EVs.

Main Results:

• CBD-EVs demonstrated structural integrity and distinct miRNA cargo.
• CBD-EVs significantly increased viability and reduced ROS in oxidative-stressed ARPE-19 cells.
• Treatment with CBD-EVs downregulated inflammation/apoptosis markers and upregulated antioxidant proteins.

Conclusions:

• miRNAs within EVs serve as biomarkers and therapeutic targets for retinal diseases.
• CBD-EVs show promise in alleviating AMD by activating the AMPK pathway.
• CBD-EVs represent a novel therapeutic strategy for AMD treatment.