Altered Lacrimal Response in Protein–kinase C deficient mice

Abstract

Abstract: : Purpose: Protein kinase C alpha (PKCα) is a key intracellular molecule signaling tear secretion by the lacrimal gland. This study evaluated the lacrimal and corneal response to desiccating environmental stress in PKCα knockout mice and their normal littermates. Methods: Tear production, tear clearance and corneal epithelial permeability to fluorescein were compared in untreated PKC deficient (–/–) and wild–type (+/+) mice and in mice exposed to low humidity and an air draft for up to 5 days. Corneal, conjunctival and lacrimal gland histology was evaluated in H&E and PAS–stained sections. Results: PKC –/– mice had significantly lower tear production and clearance and greater corneal fluorescein permeability in response to a desiccating stress than PKC +/+ mice. The lacrimal gland acinar cells of PKC –/– mice were packed with PAS positive material, which obliterated the acinar lumens. The corneal epithelium was thinner in the PKC –/– mice than in the wild–type mice. Conclusions: PKCα deficient mice showed a significantly impaired lacrimal response and greater disruption of corneal epithelial barrier function when exposed to desiccating environmental stress. The altered lacrimal function in PKC –/– mice results in a thinner corneal epithelium. These knockout mice appear to be a relevant model for studying aqueous deficient dry eye.

Keywords: cornea: tears/tear film/dry eye • cornea: epithelium • lacrimal gland