Role of α₁-adrenoceptor subtypes on corneal epithelial thickness and cell proliferation in mice

Adrenergic stimuli are important for corneal epithelial structure and healing. The purpose of the present study was to examine the hypothesis that the lack of a single α₁-adrenoceptor (α₁-AR) subtype affects corneal epithelial thickness and cell proliferation. Expression levels of α₁-AR mRNA were determined in mouse cornea using real-time PCR. In mice devoid of one of the three α₁-AR subtypes (α_1A-AR^-/-, α_1B-AR^-/-, α_1D-AR^-/-) and in wild-type controls, thickness of individual corneal layers, the number of epithelial cell layers, and average epithelial cell size were determined in cryosections. Endothelial cell density and morphology were calculated in corneal explants, and epithelial cell proliferation rate was determined with immunofluorescence microscopy. Moreover, the ultrastructure of the corneal epithelium was examined by transmission electron microscopy. Messenger RNA for all three α₁-AR subtypes was expressed in whole cornea and in corneal epithelium from wild-type mice with a rank order of abundance of α_1A ≥ α_1B > α_1D. In contrast, no α₁-AR mRNA was detected in the stroma, and only α_1B-AR mRNA was found in the Descemet endothelial complex. Remarkably, corneal epithelial thickness and mean epithelial cell size were reduced in α_1A-AR^-/- mice. Our findings suggest that the α_1A-AR exerts growth effects in mouse corneal epithelial cells.