Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6+/- mouse model of aniridia-related keratopathy
Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6+/- mouse model of aniridia-related keratopathy
复制标题
DOI：
10.1167/iovs.06-0581
复制
发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Collinson, J. Martin
中科院分区：
文献类型：
--
作者：
Kucerova, Romana;Ou, Jingxing;Collinson, J. Martin
目的. Pax 6杂合性导致的先天性无虹膜与眼表疾病（包括角膜病）相关。本研究探讨Pax 6（+/-）细胞表面糖缀合物组分的缺陷如何导致与疾病相关的异常细胞迁移表型。对来自野生型和Pax 6（+/-）同窝仔的眼睛和培养的角膜上皮细胞进行免疫组织化学、基于凝集素的组织化学、常规染色技术和蛋白质组学测定。在培养中操作野生型细胞，以复制Pax 6杂合子中发现的糖缀合物异常，并确定伤口愈合的后果。在Pax 6突变细胞中发现了多个糖缀合物缺陷。角膜上皮细胞凝集素细胞化学显示糖蛋白运输部分失败。阻断野生型角膜细胞中的细胞表面碳水化合物部分引起的伤口愈合延迟与未处理的Pax 6（+/-）细胞中观察到的相似。Pax 6（+/-）角膜上皮细胞表面糖缀合物特征的改变限制了细胞响应于创伤而启动迁移的能力。这是在培养的Pax 6（+/-）上皮细胞中观察到的伤口愈合延迟的基础。
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.