Pathophysiology of aniridia-associated keratopathy: Developmental aspects and unanswered questions

L. Latta*, F. C. Figueiredo, R. Ashery-Padan, J. M. Collinson, J. Daniels, S. Ferrari, N. Szentmáry, S. Solá, R. Shalom-Feuerstein, M. Lako, S. Xapelli, D. Aberdam, N. Lagali

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Aniridia, a rare congenital disease, is often characterized by a progressive, pronounced limbal insufficiency and ocular surface pathology termed aniridia-associated keratopathy (AAK). Due to the characteristics of AAK and its bilateral nature, clinical management is challenging and complicated by the multiple coexisting ocular and systemic morbidities in aniridia. Although it is primarily assumed that AAK originates from a congenital limbal stem cell deficiency, in recent years AAK and its pathogenesis has been questioned in the light of new evidence and a refined understanding of ocular development and the biology of limbal stem cells (LSCs) and their niche. Here, by consolidating and comparing the latest clinical and preclinical evidence, we discuss key unanswered questions regarding ocular developmental aspects crucial to AAK. We also highlight hypotheses on the potential role of LSCs and the ocular surface microenvironment in AAK. The insights thus gained lead to a greater appreciation for the role of developmental and cellular processes in the emergence of AAK. They also highlight areas for future research to enable a deeper understanding of aniridia, and thereby the potential to develop new treatments for this rare but blinding ocular surface disease.

Original languageEnglish
Pages (from-to)245-266
Number of pages22
JournalOcular Surface
Volume22
DOIs
StatePublished - Oct 2021

Funding

FundersFunder number
AAK-INSIGHT
Dr. Rolf M. Schwiete Foundation
EJP RD 2020
European Joint Programme on Rare Diseases
European Cooperation in Science and TechnologyCA18116

    Keywords

    • (LSC)
    • Aniridia
    • Aniridia animal and cellular models
    • Aniridia-associated keratopathy (AAK)
    • Anterior chamber
    • Clinical research
    • Development
    • Limbal niche
    • Limbal stem cells
    • PAX6
    • Research strategies

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