Thyroid Hormone Signaling in Retinal Development, Survival, and Disease

Thyroid hormone (TH) is essential in numerous physiological functions and developmental processes. It acts through TH receptors (TRs) to regulate gene expression. The retina is the light-sensitive tissue lining the back of the eye and functions as the first step of the visual process. Rod and cone photoreceptors are specialized sensory neurons in the retina that initiate phototransduction. Rods are responsible for dim light vision, whereas cones are responsible for daytime vision, color vision, and visual acuity. TH signaling regulates retinal development and maintenance. The requirement of TH signaling is typically manifested as its regulation in the cone maturation and expression of the light-sensing pigment protein (cone opsin). There are two components of this regulation. First, TRβ2, a TH-activated transcription factor, is expressed in immature cones and regulates cone differentiation and cone opsin expression; activation of TRβ2 suppresses the expression of short-wave-sensitive opsin 1, induces the expression of medium-wave-sensitive opsin 1, and promotes dorsal-ventral opsin patterning. Second, hypothyroid mouse models display abnormalities in cone opsin expression, supporting the necessity of TH itself in retinal development. TH has been linked to photoreceptor survival. Excessive TH signaling leads to death of developing photoreceptors in healthy and diseased retina, whereas suppressing TH signaling preserves cones in mouse models of retinal degeneration. Some eye diseases, including age-related macular degeneration, have been associated with elevated circulation TH levels. Future work should aim to better understand how TH regulates retinal development, functionality, and survival, to examine the role of TH signaling in the pathogenesis of retinal degeneration, and to explore the potential of TH signaling manipulation for photoreceptor protection. Hopefully, these knowledge bases will lead to the identification of novel strategies for retinal disease prevention and management.