Decreased, Triiodothyronine (T3) leads to Altered, retinal layer structure

Several studies have shown molecular responses to hypothyroidism that are related to eye development (Bagci et al., 2015; Houbrechts et al., 2016; Baumann et al., 2019) but the exact molecular processes linking lower TH level to disturbances of the layers in the retina is not yet fully understood. 

Both decreased as well as increased TH action has been shown to impact retinal development.

• For example, Ng et al. (2010) showed altered cone appearance in the retina following both DIO3 knockout (leading to hyperthyroidism) and THRb2 knockout (corresponding to hypothyroidism).
• Besson et al. (2020) used pharmacological treatments (T3 + iopanoic acid (IOP), NH3) to not only disrupt but also activate the TH signaling pathway. They used 10−6M T3 + (iopanoic acid) (T3 treatment) to achieve TH signal activation. Here, IOP was used as an inhibitor of deiodinase enzymes, following comparable work in mammals and amphibians, and as routinely used in fish to prevent the immediate degradation of injected T3. The combined treatment thus causes elevated T3 levels. Detected effects on retinal layers were elevated densities of bipolar cells at day 2 in surgeonfish.
• Suppressing TH signaling in retina dystrophy mouse models (a mouse model of retinal degeneration) seems to protect cone viability (Ma et al., 2014; 2016). The authors suggested that the impact of TH on cone survival is independent of its impact on cone opsin expression. The mechanism underlying the effect on cone viability has not been elucidated. 
• Bhumika et al. (2014) showed accelerated reinnervation of the optic tectum after optic nerve crush in zebrafish that had been treated with IOP or a TR antagonist. B     oth treatments cause hypothyroidism. Supplementation of T3 reduced the rate of reinnervation.

Another uncertainty lies in the systemic versus local changes in T3 levels. Although the assumed site of T3 decrease is assumed to be in the retinal layers itself, most fish early life stage studies only quantify whole body T3 levels which does not allow for making the distinction between systemic and local T3 levels.

Most knowledge comes from effects observed in developing organisms. There are some gaps in our knowledge about how TH levels affect the eyes of already fully developed organisms and/or whether they have similarly serious effects on the retinal layers. It can be assumed that the effects, if any, are weaker. Studies (Reider et al. 2014) found that layer thickness varied across ages suggesting that these retinal layers are differentially sensitive to for example MMI and/or that there are different critical periods of sensitivity of the retinal tissue.

• One feedback loop mechanism could be triggered by iodine deficiency or inhibition of iodine uptake. It appears probably that the inhibition increases the secretion of Thyroid stimulating hormone, which could stimulate the expression of the NIS-transporter. This increase in TSH could shift the ratio in favour of T3.