Deficiency of type 2 iodo‐ thyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice

What is it about?

Millions of people around the world suffer from retinal degenerative diseases, including Leber congenital amaurosis (LCA, a pediatric retinal degenerative disease) and age-related eye diseases. Rod and cone photoreceptor cells are the light-sensitive cells in the retina. Common to all retinal degenerative diseases is the damage/death of photoreceptor cells, which ultimately leads to visual impairment and loss of vision. Thyroid hormone is essential to the development and differentiation of all cells in the human body, and has been shown to regulate cone photoreceptor cell survival and death. Excessive amount of thyroid hormone causes death of cone photoreceptors in mice whereas inhibition of thyroid hormone function protects cone photoreceptors in mouse models of retinal degeneration, including LCA Rpe65-deficient mice. This work investigated the cellular mechanisms underlying how inhibition of cellular thyroid hormone production leads to cone photoreceptor protection in Rpe65-deficient mice. Rpe65-deficient mice showed an increase in cellular death pathway activity and oxidative stress responses. Inhibition of thyroid hormone production reduced these cellular events. The findings from this work suggest that thyroid hormone inhibition-induced cone protection involves inhibition of cellular death pathway activity and oxidative stress responses in the retina, and support the view that suppression of thyroid hormone activity locally in the eye may represent a strategy for cone photoreceptor protection.

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