Altered morphology and function of the lacrimal functional unit in protein kinase cα knockout mice

Zhuo Chen, Zhijie Li, Surendra Basti, William J. Farley, Stephen C. Pflugfelder

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

PURPOSE. Protein kinase C (PKC) α plays a major role in the parasympathetic neural stimulation of lacrimal gland (LG) secretion. It also has been reported to have antiapoptotic properties and to promote cell survival. Therefore, the hypothesis for the present study was that PKCα knockout ( -/-) mice have impaired ocular surface-lacrimal gland signaling, rendering them susceptible to desiccating stress and impaired corneal epithelial wound healing. In this study, the lacrimal function unit (LFU) and the stressed wound-healing response were examined in PKCα -/- mice. METHODS. In PKCα +/+ control mice and PKCα -/- mice, tear production, osmolarity, and clearance rate were evaluated before and after experimental desiccating stress. Histology and immunofluorescent staining of PKC and epidermal growth factor were performed in tissues of the LFU. Cornified envelope (CE) precursor protein expression and cell proliferation were evaluated. The time course of healing and degree of neutrophil infiltration was evaluated after corneal epithelial wounding. RESULTS. Compared with the PKCα +/+ mice, the PKCα -/- mice were noted to have significantly increased lacrimal gland weight, with enlarged, carbohydrate-rich, PAS-positive acinar cells; increased corneal epithelia permeability, with reduced CE expression; and larger conjunctival epithelial goblet cells. The PKCα -/- mice showed more rapid corneal epithelial healing, with less neutrophil infiltration and fewer proliferating cells than did the PKCα +/+ mice. CONCLUSIONS. The PKCα -/- mice showed lower tear production, which appeared to be caused by impaired secretion by the LG and conjunctival goblet cells. Despite their altered tear dynamics, the PKCα -/- mice demonstrated more rapid corneal epithelial wound healing, perhaps due to decreased neutrophil infiltration.

Original languageEnglish (US)
Pages (from-to)5592-5600
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number11
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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