Silencing Ubiquitin-Specific Peptidase 10 Alleviates Persistent Corneal Epithelial Defect in Mice

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Molecular Biology

Background:

• Persistent corneal epithelial defects lead to vision loss.
• Ubiquitin-specific peptidase 10 (USP10) is crucial for corneal wound healing and scarring.
• Current treatments for persistent defects have limitations.

Purpose of the Study:

• To investigate the efficacy of USP10-targeting self-delivering siRNA (sdRNA) in a mouse model of persistent corneal epithelial defect.
• To evaluate the impact of USP10 knockdown on corneal wound healing, scarring, and inflammation.

Main Methods:

• A mouse model was used where corneal epithelium was scraped, and defects were allowed to re-open.
• One dose of USP10-targeting sdRNA was administered post-wounding.
• Corneal morphology, epithelial stratification, hemidesmosomes, scarring, and inflammation were assessed using optical coherence tomography, histology, and immunohistochemistry.
• RNA sequencing was performed on regenerated corneal epithelium.

Main Results:

• A single USP10-targeting sdRNA dose effectively prevented wound re-opening at 28 days.
• Improved corneal morphology, normal epithelial stratification, and re-established hemidesmosomes were observed.
• Reduced scarring and inflammation (CD45+ cells) were evident.
• USP10 knockdown modulated gene expression, enhancing cell proliferation pathways and reducing scar-promoting pathways.

Conclusions:

• In vivo sdRNA targeting USP10 is a novel and effective strategy to prevent persistent corneal epithelial wound re-opening.
• This approach promotes regenerative healing by reducing scarring and inflammation.
• USP10-targeting sdRNA holds potential for treating corneal defects and other tissue repair applications.