| First Author | Ou J | Year | 2010 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 51 |
| Issue | 3 | Pages | 1415-23 |
| PubMed ID | 19933176 | Mgi Jnum | J:160407 |
| Mgi Id | MGI:4454391 | Doi | 10.1167/iovs.09-4023 |
| Citation | Ou J, et al. (2010) Cytoskeletal and cell adhesion defects in wounded and Pax6+/- corneal epithelia. Invest Ophthalmol Vis Sci 51(3):1415-23 |
| abstractText | PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
