Elsevier

The Ocular Surface

Volume 22, October 2021, Pages 245-266
The Ocular Surface

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

https://doi.org/10.1016/j.jtos.2021.09.001Get rights and content
Under a Creative Commons license
Open access

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.

Keywords

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