Thyroid hormone signaling in ocular development and diseases

Thyroid hormone (TH) signaling plays a pivotal role in maintaining metabolic homeostasis across multiple organ systems, including the eye. Proper ocular development depends on precise regulation of TH levels, as deviations from this dynamic range can result in ophthalmopathy. Emerging evidence underscores the involvement of TH signaling in various ocular pathologies, such as diabetic retinopathy. Notably, suppressing TH signaling has been shown to preserve cone photoreceptors in mouse models of retinal degeneration, highlighting the intricate interplay between TH signaling and photoreceptor viability. Additionally, the well-documented association between abnormal thyroid function and proptosis further emphasizes the critical role of TH signaling in orbital tissue homeostasis. The biological effects of TH are mediated through its binding to thyroid hormone receptors (TRs), which initiate downstream genomic and non-genomic pathways. Of particular interest is the role of deiodinases (DIOs), which modulate local TH signaling in a tissue- and temporally specific manner, independent of systemic TH levels. Despite the recognized importance of TH signaling in ophthalmopathy, significant gaps remain in our understanding of its cellular and molecular mechanisms. Future studies focusing on TH signaling within specific ocular cell lineages are essential for elucidating the underlying mechanisms and uncovering new therapeutic opportunities. This review aims to provide a comprehensive overview of TH signaling in ocular physiology and pathology, with an emphasis on advancing our understanding of its molecular mechanisms.