Investigating Cone Photoreceptor Development Using Patient-derived NRL Null Retinal Organoids

Overview

Journal Commun Biol

Specialty Biology

Date 2020 Feb 22

PMID 32081919

Citations 41

Authors

Alyssa Kallman

Elizabeth E Capowski

Jie Wang

Aniruddha M Kaushik

Alex D Jansen

Kimberly L Edwards

Liben Chen

Cynthia A Berlinicke

M Joseph Phillips

Eric A Pierce

Jiang Qian

Tza-Huei Wang

David M Gamm

Donald J Zack

Affiliations

Soon will be listed here.

Abstract

Photoreceptor loss is a leading cause of blindness, but mechanisms underlying photoreceptor degeneration are not well understood. Treatment strategies would benefit from improved understanding of gene-expression patterns directing photoreceptor development, as many genes are implicated in both development and degeneration. Neural retina leucine zipper (NRL) is critical for rod photoreceptor genesis and degeneration, with NRL mutations known to cause enhanced S-cone syndrome and retinitis pigmentosa. While murine Nrl loss has been characterized, studies of human NRL can identify important insights for human retinal development and disease. We utilized iPSC organoid models of retinal development to molecularly define developmental alterations in a human model of NRL loss. Consistent with the function of NRL in rod fate specification, human retinal organoids lacking NRL develop S-opsin dominant photoreceptor populations. We report generation of two distinct S-opsin expressing populations in NRL null retinal organoids and identify MEF2C as a candidate regulator of cone development.

Citing Articles

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