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

[aniridia]

We aimed to test previous predictions that limbal epithelial stem cells (LESCs ) are quantitatively deficient or qualitatively defective in Pax 6 (+/-) 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 Pax 6 (+/-) mosaics than WT at 15 weeks but not at 3 weeks , which excludes a developmental explanation and strengthens the prediction that Pax 6 (+/-) mice have a LESC-deficiency . To investigate how Pax 6 genotype and age affected corneal homeostasis , we compared corneal epithelial cell turnover and label-retaining cells (LRCs ; putative LESCs ) in Pax 6 (+/-) 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 Pax 6 (+/-) heterozygotes but BrdU-LRCs were also present in Pax 6 (+/-) corneas . It seems likely that Pax 6 (+/-) LRCs are not exclusively stem cells and some may be terminally differentiated CD 31 -positive blood vessel cells , which invade the Pax 6 (+/-) cornea . It was not , therefore , possible to use this approach to test the prediction that Pax 6 (+/-) 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 Pax 6 (+/-) than WT mice . This implies that epithelial cell loss is higher in Pax 6 (+/-) 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 Pax 6 (+/-) 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 .

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Diseases presenting "developmental explanation" symptom

aniridia

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