July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Notch1 Signaling Pathway in Aniridia-Related Keratopathy, Normal Fetal and Adult Human Corneas
Author Affiliations & Notes
  • Berit Byström
    Ophthalmology, Umeå University - Department of Clinical Science, Umeå, Sweden
  • Andre Vicente
    Ophthalmology, Umeå University - Department of Clinical Science, Umeå, Sweden
  • Fatima Pedrosa Domellof
    Ophthalmology, Umeå University - Department of Clinical Science, Umeå, Sweden
  • Footnotes
    Commercial Relationships   Berit Byström, None; Andre Vicente, None; Fatima Pedrosa Domellof, None
  • Footnotes
    Support  Supported by grants from Stiftelsen KMA, Cronqvists stiftelse, Ögonfonden, Swedish Research Council (K2012-63x-20399-06-3), County Council of Västerbotten (Cutting Edge Medical Research; Central ALF)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2249. doi:https://doi.org/
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    • Get Citation

      Berit Byström, Andre Vicente, Fatima Pedrosa Domellof; Notch1 Signaling Pathway in Aniridia-Related Keratopathy, Normal Fetal and Adult Human Corneas. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2249. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Notch1 is suggested to play an important role during tissue development and in differentiation of the corneal epithelial cells whereas its inhibitors Dlk1 and Numb keep these cells in an immature status. Our purpose was to evaluate the presence of these factors in aniridia-related keratopathy (ARK) and in normal fetal and adult human corneas.

Methods : Two human fetal corneas, 10 and 20 weeks of gestation, two naïve corneal buttons from patients with advanced ARK, three corneal buttons from patients with ARK undergoing re-transplantation, as well as two adult healthy control corneas were processed for immunohistochemistry using antibodies against Notch1, Dlk1 and Numb.

Results : Identical staining patterns were found for Notch1 in normal adult and fetal corneas, with staining around the basal epithelial cells and in a few streaks in the stroma. In ARK corneas, Notch1 was not detected in the pannus of the stroma. On the contrary, the pannus in ARK was labeled with antibodies against Dlk1. Dlk1 was also abundant in the epithelium and in the stroma of fetal corneas but was absent from the stroma of normal adult corneas. Numb was present in the adult normal corneas and in addition labeled the ARK and fetal corneas in a pattern resembling that of Dlk1.

Conclusions : The lack of Notch1 together with abundant Dlk1 and Numb, suggest a disturbed balance between these important factors in ARK, likely to hamper differentiation of the progenitor cell population and to be important for the pathophysiology of ARK.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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