Purchase this article with an account.
Reena Bapputty, Rose Gubitosi-Klug; Diabetes modulates iodothyronine deiodinase 2 expression in the retina. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2233.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Clinical investigations associate hypothyroidism with an increased risk for microvascular complications, yet the role of thyroid hormone in the development of diabetic retinopathy is not clearly understood. The purpose of the current study is to investigate 1) thyroid hormone activating enzyme iodothyronine deiodinase 2 (Dio2) levels ex vivo in the retinas of diabetic and non-diabetic mice, 2) Dio2 expression in vitro in retinal cells grown in high glucose conditions, 3) effect of thyroid hormone supplementation on high glucose-mediated cell death in primary mouse retinal microvascular endothelial cells (mREC).
Dio2 gene expression was measured in control and 12-week streptozotocin-induced diabetic mouse retina by RNA sequencing and Real-time PCR. Mouse retinal microvascular astrocytes and mREC were cultured in normal (5 mM) or high glucose (25 mM) and Dio2 protein level was quantified in cell lysates by western blotting. Cell death was measured by trypan blue exclusion assay.
Diabetes caused a significant decrease in Dio2 transcripts in the retina (P=0.004) and an overall 50% decrease (p=0.0001) in Dio2 gene expression in the retinas of diabetic mouse compared to non-diabetic mice. Retinal cells grown in high glucose demonstrated a significant reduction of Dio2 protein level in both mouse retinal astrocytes (p=0.002) and endothelial cells (p=0.02). Moreover, a significant protective effect of thyroid hormone supplementation on high glucose-induced endothelial cell death was observed with active hormone (T3) (P=0.0079) but not with prohormone (T4), supporting a loss of Dio2 activity in the presence of high glucose conditions.
Decreased intraretinal, active thyroid hormone level due to diabetes-induced loss of Dio2 may lead to apoptosis of both vascular and neuronal cells in the retina, a contributing factor to the pathogenesis of early diabetic retinopathy.
This is a 2021 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only