Aldehyde Dehydrogenases Expression in Corneal Epithelial Cells with Limbal Stem Cell Deficiency

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Stem Cell Biology

Background:

• Limbal stem cell deficiency (LSCD) impairs corneal epithelial regeneration.
• Aldehyde dehydrogenases (ALDHs) are crucial enzymes involved in cellular differentiation and homeostasis.
• Understanding ALDH expression in LSCD is vital for developing effective ocular surface reconstruction strategies.

Purpose of the Study:

• To investigate ALDH1A1 and ALDH1A3 expression in healthy, LSCD-affected, and CAOMECS-treated rabbit corneas.
• To explore the role of ALDHs in the regenerative capacity of corneal and oral mucosal epithelial cells.

Main Methods:

• Immunofluorescence staining and Western blot analysis were employed to assess ALDH expression.
• Rabbit models of LSCD were created and treated with CAOMECS grafts.
• Human oral mucosal and corneal epithelial cells were cultured and treated with retinoic acid.

Main Results:

• ALDH1A1 and ALDH1A3 were highly expressed in healthy corneal basal cells but upregulated in LSCD-affected conjunctivalized epithelium and stroma.
• CAOMECS grafting significantly reduced ALDH expression compared to LSCD corneas.
• Retinoic acid-induced ALDH1A3 upregulation in oral mucosal cells correlated with decreased Pax-6 expression, indicating reduced regenerative potential.

Conclusions:

• This study demonstrates, for the first time, the upregulation of ALDH1A1 and ALDH1A3 in rabbit LSCD corneas.
• CAOMECS grafting shows promise in reducing aberrant ALDH enzyme levels in reconstructed corneal epithelium.
• Targeting ALDH pathways may offer a novel therapeutic approach for LSCD treatment.