Ocular development after highly effective modulator treatment early in life

Yimin Zhu; Danni Li; Felisa Reyes-Ortega; Holly R Chinnery; Elena K Schneider-Futschik

doi:10.3389/fphar.2023.1265138

Ocular development after highly effective modulator treatment early in life

Front Pharmacol. 2023 Sep 19:14:1265138. doi: 10.3389/fphar.2023.1265138. eCollection 2023.

Authors

Yimin Zhu¹, Danni Li¹, Felisa Reyes-Ortega^{1

2}, Holly R Chinnery³, Elena K Schneider-Futschik¹

Affiliations

¹ Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia.
² Department of Ophthalmology, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
³ Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia.

Abstract

Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor-tezacaftor-ivacaftor, correct the underlying molecular defect causing CF. HEMT decreases general symptom burden by improving clinical metrics and quality of life for most people with CF (PwCF) with eligible CFTR variants. This has resulted in more pregnancies in women living with CF. All HEMT are known to be able pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of HEMT in young rats demonstrated infant cataracts, and case reports have reported the presence of congenital cataracts in early life exposure to HEMT. This article reviews the evidence for how HEMT influences the dynamic and interdependent processes of healthy and abnormal lens development in the context of HEMT exposure during pregnancy and breastfeeding, and raises questions that remain unanswered.

Keywords: CFTR modulator; catarat; cystic fibrosis; eye malformations; ocular development.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. ES-F is supported by the NHMRC (Grant ID: APP1157287) and Cystic Fibrosis Australia. FR-O is supported by the Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) Fellowship supported by Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía co-funded by Fondo Social Europeo de Andalucía 2014–2020.