Thyroid hormone levels may predict pathological changes in cone opsin expression and consequent color vision defects before detectable retinopathy

Abstract

Purpose : In rat models diabetes mellitus (DM) is characterized by a prominent degeneration of cone outer segments and an increased number of dual cones coexpressing both S and M opsins. As cone opsin expression is closely controlled by thyroid hormones, we aimed to study the possible connection between dual cones and thyroid homeostasis in diabetic rats, assess dual cone numbers in diabetic human retinas. Besides, we conducted a case control study to examine whether color vision defects in early diabetes are connected to the thyroid homeostasis.

Methods : Dual cones were counted on immunostained rat retinas of type 1 and type 2 diabetes models and postmortem human diabetic and control retinas. Blood glucose, serum TSH, fT3 and fT4 levels were measured both in rats and clinical subjects. Color vision tests were performed on 30 type 2 DM patients without clinically manifest retinopathy and 27 controls.

Results : Dual cone density increased considerably in both diabetic rat and human retinas compared to non-diabetics. Serum TSH and fT3 levels in diabetic rats did not differ from controls and did not correlate with color vision defects in patients either. In type 2 diabetic rats fT4 level was significantly lower than in controls (C) (C: 8.05±0.63 pmol/L vs. DM: 5.29±0.28 pmol/L) and almost all cones in the peripheral retina were dual in nature. In type 1 diabetic rats fT4 levels did not differ from controls (C: 8.64±0.77 pmol/L vs. DM: 7.80±2.37 pmol/L); however, there was a notable deciation in diabetes. The number of dual cones plotted against fT4 levels showed a U-shape distribution with a minimum at 8 pmol/L while at higher and lower fT4 values a prominent increase was registered. In the clinical study diabetic patients made significantly more large-scale mistakes (C: 7% vs. DM: 36.7%, p=0.014). Although the fT4 level remained within the reference range in all cases, color vision defects were more common at fT4 levels higher or lower than control average.

Conclusions : Similarly to animal models we could give evidence on increased number of dual cones in human diabetic retinas. Although in diabetic rats a connection between cone opsin expression and altered fT4 levels has been revealed, further studies with more participants are needed to confirm the predictive role of fT4 in the functional consequences of pathological opsin expression in human diabetes.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.