Lens-related ocular changes in fetal rats following in-utero exposure to elexacaftor-tezacaftor-ivacaftor

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-01-01 DOI:10.1016/j.jcf.2024.11.014

Yimin Zhu , Mengliang Wu , Danni Li , Mark Habgood , Holly R Chinnery , Elena K. Schneider-Futschik

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Abstract

Background and Objective

Elexacaftor-tezacaftor-ivacaftor (ETI) is a drug treatment for cystic fibrosis that is debatable for use in pregnant women. Fetal ocular changes following prenatal exposure and while breastfeeding to ETI have been reported. The aim of this study was to assess eye development in rat fetuses following in-utero exposure to ETI.

Design and Methods

Eyes from Sprague Dawley rats born to dams given clinically relevant ETI or sham treatment from embryonic day 12–19 (E12-E19) were investigated using histology and optical coherence tomography (OCT).

Results

Lens thickness was higher in the ETI-exposure group, as measured by OCT (p = 0.0003). Lens cavities were observed in both groups, but the median individual lens cavities area was higher in the ETI-exposed eyes (p < 0.0001), as measured by histology.

Conclusion

In-utero exposure to ETI during E12-E19 was associated with subtle changes to lens anatomy, however the mechanism and clinical significance of this observation requires further investigation.

Abstract Image

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胚胎大鼠在子宫内暴露于致敏因子-致敏因子-致敏因子后晶状体相关的眼部变化。

背景和目的：elexaftor - tezactor -ivacaftor （ETI）是一种治疗囊性纤维化的药物，在孕妇中使用尚存争议。胎儿在产前和母乳喂养时暴露于ETI后的眼部变化已有报道。本研究的目的是评估大鼠胎儿在子宫内暴露于ETI后的眼睛发育。设计和方法：采用组织学和光学相干断层扫描（OCT）技术，对胚胎12-19天（E12-E19）给予临床相关ETI或假治疗的母鼠所生的Sprague Dawley大鼠的眼睛进行观察。结果：通过OCT测量，eti暴露组的晶状体厚度更高（p = 0.0003）。两组均观察到晶状体空洞，但经组织学测量，暴露于eti的眼睛中位个体晶状体空洞面积更高（p < 0.0001）。结论：E12-E19期宫内接触ETI与晶状体解剖结构的细微变化有关，但这一观察的机制和临床意义有待进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.