Age-related macular degeneration (AMD) is characterized by a progressive death of retinal pigment epithelium (RPE) cells in the central macular region of the retina and subsequent degeneration of light-sensitive neurons (photoreceptors). Oxidative stress/damage to the RPE is recognized as the core pathogenic lesion of the disease. In this project, we study the role of thyroid hormone in RPE oxidative stress/damage and investigate whether suppression of thyroid hormone activity protects RPE against oxidative damage.
Thyroid hormone regulates cell proliferation, differentiation, and metabolism. In the eye, thyroid hormone regulates retinal development and photoreceptor viability. Recently, thyroid hormone signaling has been implicated in the pathogenesis of AMD. The population-based studies suggest that higher free serum thyroid hormone values are associated with increased risk of AMD. The objective of this project is to understand the role of thyroid hormone in AMD through oxidative damage to the retinal pigment epithelium (RPE). We investigate the hypothesis that thyroid hormone promotes oxidative stress/lesions of RPE, and that suppression of thyroid hormone activity protects RPE. We examine the effects of thyroid hormone activation on survival/death of mouse RPE. We also evaluate the effects of thyroid hormone suppression on RPE viability in mouse models of oxidative damage. We anticipate that completion of the proposed study will shed light on thyroid hormone regulation of AMD pathogenesis, which is essential to determine whether suppression of thyroid hormone signaling locally, in the retina, represents a novel strategy for RPE protection and management of AMD
First published on: August 10, 2018
Last modified on: December 19, 2024