Home > Research > Publications & Outputs > Increased corneal epithelial turnover contribut...
View graph of relations

Increased corneal epithelial turnover contributes to abnormal homeostasis in the Pax6(+/-) mouse model of aniridia

Research output: Contribution to journalJournal article

Published

Standard

Increased corneal epithelial turnover contributes to abnormal homeostasis in the Pax6(+/-) mouse model of aniridia. / Douvaras, Panagiotis; Mort, Richard L.; Edwards, Dominic; Ramaesh, Kanna; Dhillon, Baljean; Morley, Steven D.; Hill, Robert E.; West, John D.

In: PLoS ONE, Vol. 8, No. 8, e71117, 13.08.2013.

Research output: Contribution to journalJournal article

Harvard

Douvaras, P, Mort, RL, Edwards, D, Ramaesh, K, Dhillon, B, Morley, SD, Hill, RE & West, JD 2013, 'Increased corneal epithelial turnover contributes to abnormal homeostasis in the Pax6(+/-) mouse model of aniridia', PLoS ONE, vol. 8, no. 8, e71117. https://doi.org/10.1371/journal.pone.0071117

APA

Douvaras, P., Mort, R. L., Edwards, D., Ramaesh, K., Dhillon, B., Morley, S. D., Hill, R. E., & West, J. D. (2013). Increased corneal epithelial turnover contributes to abnormal homeostasis in the Pax6(+/-) mouse model of aniridia. PLoS ONE, 8(8), [e71117]. https://doi.org/10.1371/journal.pone.0071117

Vancouver

Author

Douvaras, Panagiotis ; Mort, Richard L. ; Edwards, Dominic ; Ramaesh, Kanna ; Dhillon, Baljean ; Morley, Steven D. ; Hill, Robert E. ; West, John D. / Increased corneal epithelial turnover contributes to abnormal homeostasis in the Pax6(+/-) mouse model of aniridia. In: PLoS ONE. 2013 ; Vol. 8, No. 8.

Bibtex

@article{2c2bb1834b4948a591b1a6347f417b57,
title = "Increased corneal epithelial turnover contributes to abnormal homeostasis in the Pax6(+/-) mouse model of aniridia",
abstract = "We aimed to test previous predictions that limbal epithelial stem cells (LESCs) are quantitatively deficient or qualitatively defective in Pax6(+/-) mice and decline with age in wild-type (WT) mice. Consistent with previous studies, corneal epithelial stripe patterns coarsened with age in WT mosaics. Mosaic patterns were also coarser in Pax6(+/-) mosaics than WT at 15 weeks but not at 3 weeks, which excludes a developmental explanation and strengthens the prediction that Pax6(+/-) mice have a LESC-deficiency. To investigate how Pax6 genotype and age affected corneal homeostasis, we compared corneal epithelial cell turnover and label-retaining cells (LRCs; putative LESCs) in Pax6(+/-) and WT mice at 15 and 30 weeks. Limbal BrdU-LRC numbers were not reduced in the older WT mice, so this analysis failed to support the predicted age-related decline in slow-cycling LESC numbers in WT corneas. Similarly, limbal BrdU-LRC numbers were not reduced in Pax6(+/-) heterozygotes but BrdU-LRCs were also present in Pax6(+/-) corneas. It seems likely that Pax6(+/-) LRCs are not exclusively stem cells and some may be terminally differentiated CD31-positive blood vessel cells, which invade the Pax6(+/-) cornea. It was not, therefore, possible to use this approach to test the prediction that Pax6(+/-) corneas had fewer LESCs than WT. However, short-term BrdU labelling showed that basal to suprabasal movement (leading to cell loss) occurred more rapidly in Pax6(+/-) than WT mice. This implies that epithelial cell loss is higher in Pax6(+/-) mice. If increased corneal epithelial cell loss exceeds the cell production capacity it could cause corneal homeostasis to become unstable, resulting in progressive corneal deterioration. Although it remains unclear whether Pax6(+/-) mice have LESC-deficiency, we suggest that features of corneal deterioration, that are often taken as evidence of LESC-deficiency, might occur in the absence of stem cell deficiency if corneal homeostasis is destabilised by excessive cell loss.",
keywords = "Animals, Aniridia, Cell Movement, Cell Proliferation, Disease Models, Animal, Epithelium, Corneal, Eye Proteins, Female, Genotype, Homeodomain Proteins, Homeostasis, Limbus Corneae, Male, Mice, Mice, Knockout, Mosaicism, PAX6 Transcription Factor, Paired Box Transcription Factors, Repressor Proteins, Stem Cells, Journal Article, Research Support, Non-U.S. Gov't",
author = "Panagiotis Douvaras and Mort, {Richard L.} and Dominic Edwards and Kanna Ramaesh and Baljean Dhillon and Morley, {Steven D.} and Hill, {Robert E.} and West, {John D.}",
year = "2013",
month = aug
day = "13",
doi = "10.1371/journal.pone.0071117",
language = "English",
volume = "8",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

RIS

TY - JOUR

T1 - Increased corneal epithelial turnover contributes to abnormal homeostasis in the Pax6(+/-) mouse model of aniridia

AU - Douvaras, Panagiotis

AU - Mort, Richard L.

AU - Edwards, Dominic

AU - Ramaesh, Kanna

AU - Dhillon, Baljean

AU - Morley, Steven D.

AU - Hill, Robert E.

AU - West, John D.

PY - 2013/8/13

Y1 - 2013/8/13

N2 - We aimed to test previous predictions that limbal epithelial stem cells (LESCs) are quantitatively deficient or qualitatively defective in Pax6(+/-) mice and decline with age in wild-type (WT) mice. Consistent with previous studies, corneal epithelial stripe patterns coarsened with age in WT mosaics. Mosaic patterns were also coarser in Pax6(+/-) mosaics than WT at 15 weeks but not at 3 weeks, which excludes a developmental explanation and strengthens the prediction that Pax6(+/-) mice have a LESC-deficiency. To investigate how Pax6 genotype and age affected corneal homeostasis, we compared corneal epithelial cell turnover and label-retaining cells (LRCs; putative LESCs) in Pax6(+/-) and WT mice at 15 and 30 weeks. Limbal BrdU-LRC numbers were not reduced in the older WT mice, so this analysis failed to support the predicted age-related decline in slow-cycling LESC numbers in WT corneas. Similarly, limbal BrdU-LRC numbers were not reduced in Pax6(+/-) heterozygotes but BrdU-LRCs were also present in Pax6(+/-) corneas. It seems likely that Pax6(+/-) LRCs are not exclusively stem cells and some may be terminally differentiated CD31-positive blood vessel cells, which invade the Pax6(+/-) cornea. It was not, therefore, possible to use this approach to test the prediction that Pax6(+/-) corneas had fewer LESCs than WT. However, short-term BrdU labelling showed that basal to suprabasal movement (leading to cell loss) occurred more rapidly in Pax6(+/-) than WT mice. This implies that epithelial cell loss is higher in Pax6(+/-) mice. If increased corneal epithelial cell loss exceeds the cell production capacity it could cause corneal homeostasis to become unstable, resulting in progressive corneal deterioration. Although it remains unclear whether Pax6(+/-) mice have LESC-deficiency, we suggest that features of corneal deterioration, that are often taken as evidence of LESC-deficiency, might occur in the absence of stem cell deficiency if corneal homeostasis is destabilised by excessive cell loss.

AB - We aimed to test previous predictions that limbal epithelial stem cells (LESCs) are quantitatively deficient or qualitatively defective in Pax6(+/-) mice and decline with age in wild-type (WT) mice. Consistent with previous studies, corneal epithelial stripe patterns coarsened with age in WT mosaics. Mosaic patterns were also coarser in Pax6(+/-) mosaics than WT at 15 weeks but not at 3 weeks, which excludes a developmental explanation and strengthens the prediction that Pax6(+/-) mice have a LESC-deficiency. To investigate how Pax6 genotype and age affected corneal homeostasis, we compared corneal epithelial cell turnover and label-retaining cells (LRCs; putative LESCs) in Pax6(+/-) and WT mice at 15 and 30 weeks. Limbal BrdU-LRC numbers were not reduced in the older WT mice, so this analysis failed to support the predicted age-related decline in slow-cycling LESC numbers in WT corneas. Similarly, limbal BrdU-LRC numbers were not reduced in Pax6(+/-) heterozygotes but BrdU-LRCs were also present in Pax6(+/-) corneas. It seems likely that Pax6(+/-) LRCs are not exclusively stem cells and some may be terminally differentiated CD31-positive blood vessel cells, which invade the Pax6(+/-) cornea. It was not, therefore, possible to use this approach to test the prediction that Pax6(+/-) corneas had fewer LESCs than WT. However, short-term BrdU labelling showed that basal to suprabasal movement (leading to cell loss) occurred more rapidly in Pax6(+/-) than WT mice. This implies that epithelial cell loss is higher in Pax6(+/-) mice. If increased corneal epithelial cell loss exceeds the cell production capacity it could cause corneal homeostasis to become unstable, resulting in progressive corneal deterioration. Although it remains unclear whether Pax6(+/-) mice have LESC-deficiency, we suggest that features of corneal deterioration, that are often taken as evidence of LESC-deficiency, might occur in the absence of stem cell deficiency if corneal homeostasis is destabilised by excessive cell loss.

KW - Animals

KW - Aniridia

KW - Cell Movement

KW - Cell Proliferation

KW - Disease Models, Animal

KW - Epithelium, Corneal

KW - Eye Proteins

KW - Female

KW - Genotype

KW - Homeodomain Proteins

KW - Homeostasis

KW - Limbus Corneae

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Mosaicism

KW - PAX6 Transcription Factor

KW - Paired Box Transcription Factors

KW - Repressor Proteins

KW - Stem Cells

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.pone.0071117

DO - 10.1371/journal.pone.0071117

M3 - Journal article

C2 - 23967157

VL - 8

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 8

M1 - e71117

ER -