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Retinal organoids provide unique insights into molecular signatures of inherited retinal disease throughout retinogenesis

Lookup NU author(s): Avril Watson, Professor Majlinda LakoORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2022 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society. The demand for induced pluripotent stem cells (iPSC)-derived retinal organoid and retinal pigment epithelium (RPE) models for the modelling of inherited retinopathies has increased significantly in the last decade. These models are comparable with foetal retinas up until the later stages of retinogenesis, expressing all of the key neuronal markers necessary for retinal function. These models have proven to be invaluable in the understanding of retinogenesis, particular in the context of patient-specific diseases. Inherited retinopathies are infamously described as clinically and phenotypically heterogeneous, such that developing gene/mutation-specific animal models in each instance of retinal disease is not financially or ethically feasible. Further to this, many animal models are insufficient in the study of disease pathogenesis due to anatomical differences and failure to recapitulate human disease phenotypes. In contrast, iPSC-derived retinal models provide a high throughput platform which is physiologically relevant for studying human health and disease. They also serve as a platform for drug screening, gene therapy approaches and in vitro toxicology of novel therapeutics in pre-clinical studies. One unique characteristic of stem cell-derived retinal models is the ability to mimic in vivo retinogenesis, providing unparalleled insights into the effects of pathogenic mutations in cells of the developing retina, in a highly accessible way. This review aims to give the reader an overview of iPSC-derived retinal organoids and/or RPE in the context of disease modelling of several inherited retinopathies including Retinitis Pigmentosa, Stargardt disease and Retinoblastoma. We describe the ability of each model to recapitulate in vivo disease phenotypes, validate previous findings from animal models and identify novel pathomechanisms that underpin individual IRDs.


Publication metadata

Author(s): Watson A, Lako M

Publication type: Review

Publication status: Published

Journal: Journal of Anatomy

Year: 2023

Volume: 243

Issue: 2

Pages: 186-203

Print publication date: 01/08/2023

Online publication date: 29/09/2022

Acceptance date: 06/09/2022

ISSN (print): 0021-8782

ISSN (electronic): 1469-7580

Publisher: Wiley-Blackwell Publishing Ltd

URL: https://doi.org/10.1111/joa.13768

DOI: 10.1111/joa.13768


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