Intravitreal Administration of Retinal Organoids-Derived Exosomes Alleviates Photoreceptor Degeneration in Royal...

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Molecular Biology

Background:

• Exosomes, particularly exosomal microRNAs (miRNAs), are implicated in retinal cell degeneration and retinopathies.
• Dysfunctional exosome release is linked to disease progression, making them potential biomarkers.
• Exosomal miRNAs regulate critical retinal cell functions, including photoreceptor development and visual function.

Purpose of the Study:

• To investigate the therapeutic potential of exosomes derived from human retinal organoids (Exo-ROs) in a rat model of retinal degeneration.
• To elucidate the molecular mechanisms underlying the protective effects of Exo-ROs, focusing on signaling pathways.

Main Methods:

• Generation of retinal organoids (ROs) from human induced pluripotent stem cells.
• Extraction and isolation of exosomes from ROs (Exo-ROs).
• Intravitreal injection of Exo-ROs into Royal College of Surgeons (RCS) rats, followed by assessment of retinal structure, cell apoptosis, and visual function.
• RNA sequencing and miRNA profiling to identify affected signaling pathways.

Main Results:

• Intravitreal administration of Exo-ROs significantly reduced photoreceptor apoptosis and outer nuclear layer thinning in RCS rats.
• Exo-RO treatment preserved visual function in the treated rats.
• miRNA profiling revealed that exosomal miRNAs primarily target the mitogen-activated protein kinase (MAPK) signaling pathway.
• MAPK-related gene and protein expression was notably decreased in the Exo-RO-treated group.

Conclusions:

• Exo-ROs represent a potential novel therapeutic strategy for delaying retinal degeneration.
• The therapeutic effects of Exo-ROs appear to be mediated through the modulation of the MAPK signaling pathway.
• This study highlights the potential of exosome-based therapies for treating blinding conditions like retinopathies.