Corneal abnormalities in Pax6+/- (small eye) mice mimic human aniridia-related keratopathy

T. Ramaesh, Jon Martin Collinson, K. Ramaesh, M. H. Kaufman, J. D. West, B. Dhillon

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To investigate corneal abnormalities in heterozygous Pax6(+/Sey-Neu) (Pax(6+/-), small eye) mice and compare them with aniridia-related keratopathy in PAX(6+/)- patients.

METHODS. Fetal and postnatal corneal histopathology, adult corneal thickness, and the distribution of K12-immunostained cells were compared in wild-type and Pax6(+/-) mice.

RESULTS. Prenatally, the corneal epithelium was thinner in Pax6(+/-) fetuses than wild-type littermates, but the stroma appeared irregular, hypercellular, and thickened. The anterior chamber angle was obliterated, and the iris was hypoplastic from early developmental stages. The adult Pax6(+/-) corneal epithelium was thinner, had fewer layers, and included goblet cells, indicating repopulation from conjunctival epithelium. The ocular surface was often roughened, with epithelial vacuolation and tens tissue within the stroma. The corneal stroma was thicker centrally, with an irregular lamellar alignment. Many adult Pax6(+/-) corneas were vascularized or contained cellular infiltrates, but some remained clear. Corneal degeneration was age-related: Older Pax6(+/-) mice had prominent subepithelial pannus and more goblet cells in the peripheral corneal epithelium. Cytokeratin 12 stained very weakly in the peripheral and superficial corneal epithelium in 12-month-old Pax6(+/-) mice.

CONCLUSIONS. Corneal abnormalities in Pax6(+/-) mice are similar to those in aniridia-related keratopathy in PAX6(+/-) patients. This extends the relevance of this mouse model of human aniridia to include corneal abnormalities. Incursion of goblet cells suggests impaired function of Pax6(+/-) limbal stem cells, abnormal expression of cytokeratin 12 may result in greater epithelial fragility, and corneal opacities in older mice may reflect poor wound-healing responses to accumulated environmental insults.

Original languageEnglish
Pages (from-to)1871-1878
Number of pages7
JournalInvestigative Ophthalmology & Visual Science
Volume44
Issue number5
DOIs
Publication statusPublished - May 2003

Keywords

  • metalloproteinase gelatinase-B
  • homeobox-containing gene
  • epithelial stem-cells
  • midbrain crest cells
  • nasal development
  • ocular surface
  • PAX6 gene
  • expression
  • mutation
  • migration

Cite this

Corneal abnormalities in Pax6+/- (small eye) mice mimic human aniridia-related keratopathy. / Ramaesh, T.; Collinson, Jon Martin; Ramaesh, K.; Kaufman, M. H.; West, J. D.; Dhillon, B.

In: Investigative Ophthalmology & Visual Science, Vol. 44, No. 5, 05.2003, p. 1871-1878.

Research output: Contribution to journalArticle

Ramaesh, T. ; Collinson, Jon Martin ; Ramaesh, K. ; Kaufman, M. H. ; West, J. D. ; Dhillon, B. / Corneal abnormalities in Pax6+/- (small eye) mice mimic human aniridia-related keratopathy. In: Investigative Ophthalmology & Visual Science. 2003 ; Vol. 44, No. 5. pp. 1871-1878.
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abstract = "PURPOSE. To investigate corneal abnormalities in heterozygous Pax6(+/Sey-Neu) (Pax(6+/-), small eye) mice and compare them with aniridia-related keratopathy in PAX(6+/)- patients.METHODS. Fetal and postnatal corneal histopathology, adult corneal thickness, and the distribution of K12-immunostained cells were compared in wild-type and Pax6(+/-) mice.RESULTS. Prenatally, the corneal epithelium was thinner in Pax6(+/-) fetuses than wild-type littermates, but the stroma appeared irregular, hypercellular, and thickened. The anterior chamber angle was obliterated, and the iris was hypoplastic from early developmental stages. The adult Pax6(+/-) corneal epithelium was thinner, had fewer layers, and included goblet cells, indicating repopulation from conjunctival epithelium. The ocular surface was often roughened, with epithelial vacuolation and tens tissue within the stroma. The corneal stroma was thicker centrally, with an irregular lamellar alignment. Many adult Pax6(+/-) corneas were vascularized or contained cellular infiltrates, but some remained clear. Corneal degeneration was age-related: Older Pax6(+/-) mice had prominent subepithelial pannus and more goblet cells in the peripheral corneal epithelium. Cytokeratin 12 stained very weakly in the peripheral and superficial corneal epithelium in 12-month-old Pax6(+/-) mice.CONCLUSIONS. Corneal abnormalities in Pax6(+/-) mice are similar to those in aniridia-related keratopathy in PAX6(+/-) patients. This extends the relevance of this mouse model of human aniridia to include corneal abnormalities. Incursion of goblet cells suggests impaired function of Pax6(+/-) limbal stem cells, abnormal expression of cytokeratin 12 may result in greater epithelial fragility, and corneal opacities in older mice may reflect poor wound-healing responses to accumulated environmental insults.",
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TY - JOUR

T1 - Corneal abnormalities in Pax6+/- (small eye) mice mimic human aniridia-related keratopathy

AU - Ramaesh, T.

AU - Collinson, Jon Martin

AU - Ramaesh, K.

AU - Kaufman, M. H.

AU - West, J. D.

AU - Dhillon, B.

PY - 2003/5

Y1 - 2003/5

N2 - PURPOSE. To investigate corneal abnormalities in heterozygous Pax6(+/Sey-Neu) (Pax(6+/-), small eye) mice and compare them with aniridia-related keratopathy in PAX(6+/)- patients.METHODS. Fetal and postnatal corneal histopathology, adult corneal thickness, and the distribution of K12-immunostained cells were compared in wild-type and Pax6(+/-) mice.RESULTS. Prenatally, the corneal epithelium was thinner in Pax6(+/-) fetuses than wild-type littermates, but the stroma appeared irregular, hypercellular, and thickened. The anterior chamber angle was obliterated, and the iris was hypoplastic from early developmental stages. The adult Pax6(+/-) corneal epithelium was thinner, had fewer layers, and included goblet cells, indicating repopulation from conjunctival epithelium. The ocular surface was often roughened, with epithelial vacuolation and tens tissue within the stroma. The corneal stroma was thicker centrally, with an irregular lamellar alignment. Many adult Pax6(+/-) corneas were vascularized or contained cellular infiltrates, but some remained clear. Corneal degeneration was age-related: Older Pax6(+/-) mice had prominent subepithelial pannus and more goblet cells in the peripheral corneal epithelium. Cytokeratin 12 stained very weakly in the peripheral and superficial corneal epithelium in 12-month-old Pax6(+/-) mice.CONCLUSIONS. Corneal abnormalities in Pax6(+/-) mice are similar to those in aniridia-related keratopathy in PAX6(+/-) patients. This extends the relevance of this mouse model of human aniridia to include corneal abnormalities. Incursion of goblet cells suggests impaired function of Pax6(+/-) limbal stem cells, abnormal expression of cytokeratin 12 may result in greater epithelial fragility, and corneal opacities in older mice may reflect poor wound-healing responses to accumulated environmental insults.

AB - PURPOSE. To investigate corneal abnormalities in heterozygous Pax6(+/Sey-Neu) (Pax(6+/-), small eye) mice and compare them with aniridia-related keratopathy in PAX(6+/)- patients.METHODS. Fetal and postnatal corneal histopathology, adult corneal thickness, and the distribution of K12-immunostained cells were compared in wild-type and Pax6(+/-) mice.RESULTS. Prenatally, the corneal epithelium was thinner in Pax6(+/-) fetuses than wild-type littermates, but the stroma appeared irregular, hypercellular, and thickened. The anterior chamber angle was obliterated, and the iris was hypoplastic from early developmental stages. The adult Pax6(+/-) corneal epithelium was thinner, had fewer layers, and included goblet cells, indicating repopulation from conjunctival epithelium. The ocular surface was often roughened, with epithelial vacuolation and tens tissue within the stroma. The corneal stroma was thicker centrally, with an irregular lamellar alignment. Many adult Pax6(+/-) corneas were vascularized or contained cellular infiltrates, but some remained clear. Corneal degeneration was age-related: Older Pax6(+/-) mice had prominent subepithelial pannus and more goblet cells in the peripheral corneal epithelium. Cytokeratin 12 stained very weakly in the peripheral and superficial corneal epithelium in 12-month-old Pax6(+/-) mice.CONCLUSIONS. Corneal abnormalities in Pax6(+/-) mice are similar to those in aniridia-related keratopathy in PAX6(+/-) patients. This extends the relevance of this mouse model of human aniridia to include corneal abnormalities. Incursion of goblet cells suggests impaired function of Pax6(+/-) limbal stem cells, abnormal expression of cytokeratin 12 may result in greater epithelial fragility, and corneal opacities in older mice may reflect poor wound-healing responses to accumulated environmental insults.

KW - metalloproteinase gelatinase-B

KW - homeobox-containing gene

KW - epithelial stem-cells

KW - midbrain crest cells

KW - nasal development

KW - ocular surface

KW - PAX6 gene

KW - expression

KW - mutation

KW - migration

U2 - 10.1167/iovs.02-0576

DO - 10.1167/iovs.02-0576

M3 - Article

VL - 44

SP - 1871

EP - 1878

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

SN - 0146-0404

IS - 5

ER -