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Jingxing Ou, Christina Lowes, J. Martin Collinson; Cytoskeletal and Cell Adhesion Defects in Wounded and Pax6+/− Corneal Epithelia. Invest. Ophthalmol. Vis. Sci. 2010;51(3):1415-1423. doi: 10.1167/iovs.09-4023.
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PAX6 heterozygosity (PAX6 +/−) causes aniridia and aniridia-related keratopathy (ARK) in humans, but the pathway from gene dosage deficiency to clinical disease has not been fully characterized. Recently, the authors suggested a model of a chronic wound state exacerbated by oxidative stress, showed the barrier function of Pax6 +/− corneas is compromised and suggested Pax6 +/− corneas show the molecular signature of a perpetual wound-healing state.
Pax6 +/− mice were used as a model for Pax6-related corneal diseases and in vivo wound-healing assays. Immunohistochemistry and electron microscopy analyses were performed on mutant and wounded corneas.
This work reports defects in keratin, desmoplakin, and actin-based cytoskeletal structures in Pax6 +/− cells. During wild-type corneal reepithelialization, cell fissures and desquamation, intracellular vesicles, intercellular gaps, and filopodialike structures were apparent, similar to the phenotypes seen in “unwounded” Pax6 +/− corneal epithelia. Pax6 +/− cells and wounded wild-type cells showed changed patterns of desmoplakin and actin localization. Protein oxidation and ERK1/2 and p38 MAPK phosphorylation were barely detected in the basal cells of intact wild-type corneal epithelia, but they were found in basal wild-type cells near the wound edge and throughout Pax6 +/− corneal epithelia.
These data show that cell junctions and cytoskeleton organization are dynamically remodeled in vivo by wounding and in Pax6 +/− corneas. This apparent wound-healing phenotype contributes to the clinical aspects of ARK.
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