Abstract
Limbal stem cells are essential for continuous corneal regeneration and injury repair. METTL3-catalyzed N6-methyladenosine (m6A) mRNA modifications are involved in many biological processes and play a specific role in stem cell regeneration, while the role of m6A modifications in corneal injury repair remains unknown. In this study, we generated a limbal stem cell-specific METTL3 knockout mouse model and studied the role of m6A in repairing corneal injury caused by alkali burn. The results showed that METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DDIT4 as m6A targets. Our study reveals the essential functions of m6A RNA modification in regulating injury repair and provides novel insights for clinical therapy of corneal diseases.
Highlights
The integrity and function of the cornea depend on the selfrenewing properties of the corneal epithelium
The deletion of METTL3 in keratin 14-positive cells was confirmed by keratin 14 (K14) and METTL3 immunofluorescence staining (Figures 1(c) and 1(d))
Through sodium fluorescein staining of mouse corneal cell layers, we found that one day after the injury, eyes in the WT mice showed a wide range of diffuse patch staining, indicating the defective function to exclude dye penetration due to corneal injury
Summary
The integrity and function of the cornea depend on the selfrenewing properties of the corneal epithelium. The corneal limbus locates at the junction of the cornea, the conjunctiva, and the sclera. Misregulation of limbal stem cells often results in visual defects, and regulation of limbal stem cell regeneration is a promising strategy for treating eye diseases [2, 3]. Limbal stem cells maintain the corneal physiology and biochemistry and regulate its nutrition, immune response, and integrity. Keratin 14 (K14) is a marker of limbal stem cells, and K14CreER was observed migrating centripetally from the limbus to the central cornea. Studying proliferation, differentiation, and the regulatory mechanism of limbal stem cells can provide new methods and insights into treating corneal defects in various ocular diseases
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