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Publication : Altered morphology and function of the lacrimal functional unit in protein kinase C{alpha} knockout mice.

First Author  Chen Z Year  2010
Journal  Invest Ophthalmol Vis Sci Volume  51
Issue  11 Pages  5592-600
PubMed ID  20505191 Mgi Jnum  J:171403
Mgi Id  MGI:4949832 Doi  10.1167/iovs.09-4562
Citation  Chen Z, et al. (2010) Altered morphology and function of the lacrimal functional unit in protein kinase C{alpha} knockout mice. Invest Ophthalmol Vis Sci 51(11):5592-600
abstractText  PURPOSE: Protein kinase C (PKC) alpha 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 PKCalpha 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 PKCalpha(-/-) mice. METHODS: In PKCalpha(+/+) control mice and PKCalpha(-/-) 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 PKCalpha(+/+) mice, the PKCalpha(-/-) 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 PKCalpha(-/-) mice showed more rapid corneal epithelial healing, with less neutrophil infiltration and fewer proliferating cells than did the PKCalpha(+/+) mice. CONCLUSIONS: The PKCalpha(-/-) 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 PKCalpha(-/-) mice demonstrated more rapid corneal epithelial wound healing, perhaps due to decreased neutrophil infiltration.
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