The mechanisms, epidemiology, and clinical implications of thyroid hormones and age-related macular degeneration: a narrative review

TL;DR

This paper reviews how thyroid hormones may contribute to age-related macular degeneration, a major cause of vision loss in older adults.

Contribution

The paper integrates experimental, genetic, and clinical evidence to propose a role for thyroid hormones in AMD pathogenesis.

Findings

Excessive thyroid hormone signaling worsens retinal damage in AMD models.

Higher free thyroxine levels are genetically and clinically linked to increased AMD risk.

Thyroid hormone inhibition shows protective effects in retinal cells.

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among older adults. Thyroid hormones (THs) are essential endocrine regulators of development and metabolic homeostasis, and increasing evidence suggests that TH signaling is involved in retinal physiology and AMD pathogenesis. Experimental studies have demonstrated that excessive TH signaling exacerbates oxidative stress, mitochondrial dysfunction, and apoptosis in retinal pigment epithelium (RPE) cells and photoreceptors, whereas inhibition of TH signaling confers retinal protection in animal models of dry AMD. Genetic evidence from Mendelian randomization analyses further indicates that genetically predicted higher free thyroxine (FT4), per one standard deviation increase, is associated with an increased risk of AMD (OR 1.19, 95% CI 1.06–1.33), while no causal association has been established for thyroid-stimulating hormone (TSH). Consistently, large population-based cohort studies, including the Rotterdam Study, have reported a positive association between circulating FT4 levels and the incidence of AMD. In this narrative review, we summarize and critically evaluate recent advances from basic experimental, genetic, and clinical studies on the relationship between thyroid hormones and AMD, discuss potential biological mechanisms underlying this association, and highlight current limitations and future research directions.

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