Inhibiting miR-195-5p Induces Proliferation of Human Corneal Endothelial Cells

Area of Science:

• Ophthalmology
• Molecular Biology
• Cell Biology

Background:

• Human corneal endothelial cells (HCEnCs) maintain corneal transparency for clear vision.
• Dysfunction of HCEnCs leads to irreversible corneal blindness.
• Identifying factors limiting HCEnC proliferation is crucial for developing regenerative therapies.

Purpose of the Study:

• To investigate the inhibitory effect of miR-195-5p on HCEnC proliferation.
• To explore the potential of modulating miR-195-5p for treating corneal endothelial dysfunction.

Main Methods:

• Cultured human corneal endothelial cell line (HCEC-12) and primary HCEnCs with miR-195-5p modulators.
• Analyzed miR-195-5p expression in human corneal tissues (cadaveric, FECD) and animal models (pig, mouse, rabbit) using RT-PCR.
• Assessed HCEnC proliferation, viability, apoptosis, and marker expression after miR-195-5p inhibition.

Main Results:

• miR-195-5p was upregulated in Fuchs endothelial corneal dystrophy (FECD) tissues but downregulated in proliferative animal CEnCs.
• Inhibiting miR-195-5p significantly increased HCEnC proliferation, cell doubling, and wound healing rates.
• Inhibition of miR-195-5p improved cell viability, reduced apoptosis, and modulated key endothelial markers (ZO-1, Na+/K+-ATPase, Ki-67).

Conclusions:

• miR-195-5p expression restricts HCEnC proliferation in both healthy and FECD cells.
• Inhibiting miR-195-5p can induce HCEnC proliferation, suggesting a therapeutic strategy for FECD.
• Targeting miR-195-5p with anti-miR therapy offers a promising avenue for regenerative ophthalmology.