Abstract
Purpose :
Prior investigations demonstrated that iodothyronine deiodinase (Dio2) gene expression, the enzyme that converts thyroxine (T4) to triiodothyronine (T3), is decreased in the mouse retina during diabetes. As well, exogenous T3 supplementation of primary mouse retinal endothelial cells (mREC) in culture prevented high-glucose induced cell death. Yet, investigations of Dio2 function in mREC under high glucose conditions and the mechanism underlying thyroid hormone effects on the retinal microvasculature have not been studied.
Methods :
T4 and T3 were simultaneously quantified by liquid chromatography-tandem mass spectrometry. mREC were cultured in physiologic (5 mM) or high glucose (30 mM). Cell lysates were analyzed after five days in culture for T4 and T3 concentrations. Endothelial nitric oxide synthase (eNOS) was detected in cell lysates by western blotting.
Results :
When mREC were grown in the presence of high glucose, intracellular production of T3 decreased and T4 increased leading to a significantly increased T4/T3 ratio (P=0.007) when compared to cells grown in physiologic glucose. Supplementation of cells with T3, but not T4, increased T3 in mREC (P=0.007), consistent with suppressed Dio2 function under high glucose. Similarly, T3, but not T4, supplementation prevented the high glucose-induced rise in eNOS level (P=0.03).
Conclusions :
Our study indicates that high glucose during diabetes may cause decreased intracellular T3 concentrations in retinal cells and that may lead to alterations in vascular tone and function, thereby contributing to the pathogenesis of diabetic retinopathy.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.