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

Lorenz  Latta; F. C.  Figueiredo; R.  Ashery-Padan; Jon Collinson; J. Daniels; Stefano Ferrari; N.  Szentmáry; S. Solá; R.  Shalom-Feuerstein; M.  Lako; S.  Xapelli; D. Aberdam; N. Lagali

doi:10.1016/j.jtos.2021.09.001

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

Lorenz Latta^* (Corresponding Author), F. C. Figueiredo, R. Ashery-Padan, Jon Collinson, J. Daniels, Stefano Ferrari, N. Szentmáry, S. Solá, R. Shalom-Feuerstein, M. Lako, S. Xapelli, D. Aberdam^* (Corresponding Author), N. Lagali^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	245-266
Number of pages	22
Journal	The Ocular Surface
Volume	22
Early online date	23 Sept 2021
DOIs	https://doi.org/10.1016/j.jtos.2021.09.001
Publication status	Published - Oct 2021

Bibliographical note

This review is based upon work from the Work Group5 of the COST
Action CA18116 (Aniridia: networking to address an unmet medical, scientific, and societal challenge), supported by COST (European Cooperation in Science and Technology). The European Joint Programme on Rare Diseases (EJP RD 2020) is acknowledged for its support to NL, LL, DA, MJC, NS, RAP (AAK-INSIGHT). The work of LL and NS at the Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research at Saarland University, Germany was supported by the Dr. Rolf M. Schwiete Foundation.

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

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Latta_etal_TOS_Pathophysiology_Aniridia_Associated_VoR
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Cite this

Latta, L., Figueiredo, F. C., Ashery-Padan, R., Collinson, J., Daniels, J., Ferrari, S., Szentmáry, N., Solá, S., Shalom-Feuerstein, R., Lako, M., Xapelli, S., Aberdam, D., & Lagali, N. (2021). Pathophysiology of aniridia-associated keratopathy: developmental aspects and unanswered questions. The Ocular Surface, 22, 245-266. https://doi.org/10.1016/j.jtos.2021.09.001

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title = "Pathophysiology of aniridia-associated keratopathy: developmental aspects and unanswered questions",

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",

author = "Lorenz Latta and Figueiredo, {F. C.} and R. Ashery-Padan and Jon Collinson and J. Daniels and Stefano Ferrari and N. Szentm{\'a}ry and S. Sol{\'a} and R. Shalom-Feuerstein and M. Lako and S. Xapelli and D. Aberdam and N. Lagali",

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AU - Latta, Lorenz

AU - Figueiredo, F. C.

AU - Ashery-Padan, R.

AU - Collinson, Jon

AU - Daniels, J.

AU - Ferrari, Stefano

AU - Szentmáry, N.

AU - Solá, S.

AU - Shalom-Feuerstein, R.

AU - Lako, M.

AU - Xapelli, S.

AU - Aberdam, D.

AU - Lagali, N.

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N2 - 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.

AB - 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.

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KW - Anterior chamber

KW - development

KW - limbal stem cells (LSC)

KW - Aniridia

KW - aniridia animal and cellular models

KW - Clinical Research

KW - research strategies

KW - limbal niche

U2 - 10.1016/j.jtos.2021.09.001

DO - 10.1016/j.jtos.2021.09.001

M3 - Article

SN - 1542-0124

VL - 22

SP - 245

EP - 266

JO - The Ocular Surface

JF - The Ocular Surface

ER -

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

Abstract

Bibliographical note

Keywords

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