To the extent possible under law, AOP-Wiki has waived all copyright and related or neighboring rights to KER:2373
Decreased, Triiodothyronine (T3) in serum leads to Altered, retinal layer structure
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Thyroperoxidase inhibition leading to increased mortality via altered retinal layer structure||adjacent||Lucia Vergauwen (send email)||Under development: Not open for comment. Do not cite|
Life Stage Applicability
Key Event Relationship Description
It is known that thyroid hormones (THs) regulate eye development in vertebrates (reviewed by Darras 20151). Therefore, decreased T3 levels in serum during eye development are likely to lead to structural and morphological alterations of the eyes.
Evidence Supporting this KER
THs, TH receptors, and deiodinase enzymes are important for eye and retinal development in vertebrates. Dio either inactivate T3 or convert T4 to T3, consequently playing a central role in regulating TH levels in target tissues. In zebrafish, TH receptors and dio enzymes have been localized in the retina from 24 hpf onwards, probably regulating the differentiation of retinal structures and photoreceptors.
It is known from amphibians that when TH levels start to rise at the beginning of metamorphosis, the morphology of the eyes starts changing. In chicken, the developing eye shows a dynamic expression pattern of D2 and D3, probably regulating photoreceptor differentiation and cornea development (reviewed by Darras 2015).
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Life-stage applicability: all studies on TH-regulated eye morphology and structure are performed during vertebrate development from embryo to adult. It appears that TH-changes at adult staged do not have an impact.
1. Darras VM, Houbrechts AM, Van Herck SLJ. Intracellular thyroid hormone metabolism as a local regulator of nuclear thyroid hormone receptor-mediated impact on vertebrate development. Biochim Biophys Acta - Gene Regul Mech. 2015;1849(2):130-141. doi:10.1016/j.bbagrm.2014.05.004
2. Houbrechts AM, Delarue J, Gabriëls IJ, Sourbron J, Darras VM. Permanent deiodinase type 2 Deficiency strongly perturbs zebrafish development, growth, and fertility. Endocrinology. 2016;157(9):3668-3681. doi:10.1210/en.2016-1077
3. Gamborino MJ, Sevilla-Romero E, Muñoz A, Hernández-Yago J, Renau-Piqueras J, Pinazo-Durán MD. Role of thyroid hormone in craniofacial and eye development using a rat model. Ophthalmic Res. 2001;33(5):283-291. doi:10.1159/000055682
4. Quesada-García A, Encinas P, Valdehita A, et al. Thyroid active agents T3 and PTU differentially affect immune gene transcripts in the head kidney of rainbow trout (Oncorynchus mykiss). Aquat Toxicol. 2016;174:159-168. doi:10.1016/j.aquatox.2016.02.016