Cytoskeletal and cell adhesion defects in wounded and Pax6+/- corneal epithelia

Jingxing Ou, Christina Lowes, J Martin Collinson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1415-1423
Number of pages9
JournalInvestigative Ophthalmology & Visual Science
Volume51
Issue number3
Early online date20 Nov 2009
DOIs
Publication statusPublished - Mar 2010

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Corneal Epithelium
Cell Adhesion
Aniridia
Cornea
Desmoplakins
Wound Healing
Actins
Corneal Diseases
Phenotype
Intercellular Junctions
Gene Dosage
Wounds and Injuries
p38 Mitogen-Activated Protein Kinases
Keratins
Cytoskeleton
Electron Microscopy
Oxidative Stress
Immunohistochemistry
Phosphorylation
Proteins

Cite this

Cytoskeletal and cell adhesion defects in wounded and Pax6+/- corneal epithelia. / Ou, Jingxing; Lowes, Christina; Collinson, J Martin.

In: Investigative Ophthalmology & Visual Science, Vol. 51, No. 3, 03.2010, p. 1415-1423.

Research output: Contribution to journalArticle

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abstract = "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.",
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