PURPOSE: Congenital aniridia due to heterozygosity for Pax6 is associated with ocular surface disease, including keratopathy. This study investigated how defects in glycoconjugate component of the cell surface of Pax6+/- could cause the abnormal cellular migration phenotypes associated with the disease. METHODS: Immunohistochemistry, lectin-based histochemistry, conventional staining techniques, and proteomic assays were performed on eyes and cultured corneal epithelial cells from wild-type and Pax6+/- littermates. Wild-type cells were manipulated in culture to replicate the glycoconjugate abnormalities found in Pax6 heterozygotes and determine the consequences for wound healing. RESULTS: Multiple glycoconjugate defects were found in Pax6-mutant cells. Lectin cytochemistry of corneal epithelial cells suggested a partial failure of glycoprotein trafficking. Blocking cell surface carbohydrate moieties in wild-type corneal cells caused wound-healing delays similar to those seen in untreated Pax6+/- cells. CONCLUSIONS: Alterations to the cell surface glycoconjugate signature of Pax6+/- corneal epithelia restrict the ability of cells to initiate migration in response to wounding. This underlies the observed wound-healing delay in cultured Pax6+/- epithelia.
PURPOSE:Congenital aniridia due to heterozygosity for Pax6 is associated with ocular surface disease, including keratopathy. This study investigated how defects in glycoconjugate component of the cell surface of Pax6+/- could cause the abnormal cellular migration phenotypes associated with the disease. METHODS: Immunohistochemistry, lectin-based histochemistry, conventional staining techniques, and proteomic assays were performed on eyes and cultured corneal epithelial cells from wild-type and Pax6+/- littermates. Wild-type cells were manipulated in culture to replicate the glycoconjugate abnormalities found in Pax6 heterozygotes and determine the consequences for wound healing. RESULTS: Multiple glycoconjugate defects were found in Pax6-mutant cells. Lectin cytochemistry of corneal epithelial cells suggested a partial failure of glycoprotein trafficking. Blocking cell surface carbohydrate moieties in wild-type corneal cells caused wound-healing delays similar to those seen in untreated Pax6+/- cells. CONCLUSIONS: Alterations to the cell surface glycoconjugate signature of Pax6+/- corneal epithelia restrict the ability of cells to initiate migration in response to wounding. This underlies the observed wound-healing delay in cultured Pax6+/- epithelia.
Authors: N S Pellegata; J L Dieguez-Lucena; T Joensuu; S Lau; K T Montgomery; R Krahe; T Kivelä; R Kucherlapati; H Forsius; A de la Chapelle Journal: Nat Genet Date: 2000-05 Impact factor: 38.330
Authors: Caroline O Adeoti; Adebimpe A Afolabi; Adeyinka A Afolabi; Adeyinka O Ashaye; Adebimpe O Ashaye; Adenike O Adeoye Journal: Clin Ophthalmol Date: 2010-10-05
Authors: Richard L Mort; Adam J Bentley; Francis L Martin; J Martin Collinson; Panagiotis Douvaras; Robert E Hill; Steven D Morley; Nigel J Fullwood; John D West Journal: PLoS One Date: 2011-12-29 Impact factor: 3.240
Authors: Panagiotis Douvaras; Richard L Mort; Dominic Edwards; Kanna Ramaesh; Baljean Dhillon; Steven D Morley; Robert E Hill; John D West Journal: PLoS One Date: 2013-08-13 Impact factor: 3.240