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Altered Signaling Pathways in Aniridia-Related Keratopathy
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.ORCID iD: 0000-0002-7240-6515
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 13, p. 5531-5541Article in journal (Refereed) Published
Abstract [en]

PURPOSE. To study the Notch1, Wnt/beta-catenin, sonic hedgehog (SHH), and mammalian target of rapamycin (mTOR) cell signaling pathways in naive and surgically treated corneas of aniridia cases with advanced aniridia-related keratopathy (ARK).

METHODS. Two naive corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation, and two adult healthy control corneas were processed for immunohistochemistry in this descriptive study. Antibodies specific against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta-catenin), SHH (glioma-associated oncogene homolog [Gli1]; Hes1), and mTOR (mTOR1; ribosomal protein S6 [rpS6]) signaling pathways were used as well as antibodies against PAX6 and keratin 13 (Krt13).

RESULTS. All ARK corneas presented signs of conjunctivalization and analogous signaling pathway changes in the subepithelial pannus and epithelium, with decreased detection of the Notch1 signaling pathway and an increased presence of the Notch1 inhibitors Numb and Dlk1. Increased detections of Wnt/beta-catenin (enhanced presence of Wnt5a, Wnt7a, and beta-catenin), SHH (detection of Gli1 and Hes1), and mTOR (identification of mTOR and rpS6) signaling pathways were found in the subepithelial pannus and epithelium of all ARK corneas, when compared with normal controls.

CONCLUSIONS. The similarity in pathway alterations found in all ARK corneas, irrespective of limbal stem cell transplantation, further supports the discussion on the role of host-specific factors and limbal stem cell deficiency in ARK.

Place, publisher, year, edition, pages
The Association for Research in Vision and Ophthalmology , 2018. Vol. 59, no 13, p. 5531-5541
Keywords [en]
aniridia-related keratopathy, signaling pathways, keratoplasty, keratolimbal allograft, limbal stem cell deficiency, PAX6, sonic hedgehog, mTOR, Wnt, Notch1
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:umu:diva-155119DOI: 10.1167/iovs.18-25175ISI: 000452609300004PubMedID: 30480741OAI: oai:DiVA.org:umu-155119DiVA, id: diva2:1276576
Funder
Swedish Research Council, 2015-02438Västerbotten County CouncilAvailable from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved

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Vicente, AndréByström, BeritDomellöf, Fatima Pedrosa

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