Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6(+/-) mouse model of aniridia-related keratopathy

Romana Kucerova; Jingxing Ou; Diane Lawson; Lucy J. Leiper; J. Martin Collinson

doi:10.1167/iovs.06-0581

Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6(+/-) mouse model of aniridia-related keratopathy

Romana Kucerova, Jingxing Ou, Diane Lawson, Lucy J. Leiper, J. Martin Collinson

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	5276-5282
Number of pages	7
Journal	Investigative Ophthalmology & Visual Science
Volume	47
Issue number	12
DOIs	https://doi.org/10.1167/iovs.06-0581
Publication status	Published - Dec 2006

Keywords

metalloproteinase gelatinase B
heparan-sulfate proteoglycans
small-eye
expression
PAX6
gene
lens
differentiation
morphogenesis
regeneration

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@article{c8d909fd07ef452b8974b74fddd1c557,

title = "Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6(+/-) mouse model of aniridia-related keratopathy",

abstract = "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.",

keywords = "metalloproteinase gelatinase B, heparan-sulfate proteoglycans, small-eye, expression, PAX6, gene, lens, differentiation, morphogenesis, regeneration",

author = "Romana Kucerova and Jingxing Ou and Diane Lawson and Leiper, {Lucy J.} and Collinson, {J. Martin}",

year = "2006",

month = dec,

doi = "10.1167/iovs.06-0581",

language = "English",

volume = "47",

pages = "5276--5282",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "12",

}

TY - JOUR

T1 - Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6(+/-) mouse model of aniridia-related keratopathy

AU - Kucerova, Romana

AU - Ou, Jingxing

AU - Lawson, Diane

AU - Leiper, Lucy J.

AU - Collinson, J. Martin

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

KW - metalloproteinase gelatinase B

KW - heparan-sulfate proteoglycans

KW - small-eye

KW - expression

KW - PAX6

KW - gene

KW - lens

KW - differentiation

KW - morphogenesis

KW - regeneration

U2 - 10.1167/iovs.06-0581

DO - 10.1167/iovs.06-0581

M3 - Article

VL - 47

SP - 5276

EP - 5282

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 12

ER -

Cell surface glycoconjugate abnormalities and corneal epithelial wound healing in the Pax6(+/-) mouse model of aniridia-related keratopathy

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Keywords

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