title: Altered morphology and function of the lacrimal functional unit in protein kinase C{alpha} knockout mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, The Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
authors.forename: Surendra
authors.initials: S
authors.lastname: Basti
authors.forename: William J
authors.initials: WJ
authors.lastname: Farley
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
mesh_terms: D000818:Animals; D003911:Dextrans / Q000378:metabolism; D015352:Dry Eye Syndromes / Q000201:enzymology* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism; D019573:Epithelium, Corneal / Q000502:physiology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007765:Lacrimal Apparatus / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D009994:Osmolar Concentration; D010539:Permeability; D051571:Protein Kinase C-alpha / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D013666:Tears / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D003911:Dextrans; D004815:Epidermal Growth Factor; D012964:Sodium; D051571:Protein Kinase C-alpha