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Hongwei Ma, Fan Yang, Xi-Qin Ding; Inhibition of Thyroid Hormone Signaling Protects Photoreceptors from Oxidative Damage and Cell Death Induced by Sodium Iodate. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1295.
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Thyroid hormone (TH) regulates cell proliferation, differentiation, and metabolism. Recent studies have shown that higher TH levels were associated with increased risk of age-related macular degeneration (AMD), a disease characterized by oxidative damage/progressive cell dystrophy of the retinal pigment epithelium and photoreceptors. This work investigated whether inhibition of TH signaling protects photoreceptors in mice after oxidative stress challenge.
C57BL/6 mice received antithyroid drug treatment via drinking water (1% sodium perchlorate monohydrate and 0.05% methomazole) for 13 days, beginning at postnatal day 20 (P20), and received a single injection of sodium iodate (NaIO3, 30 mg/kg, i.p.) at P30. Thra1-/-, Thrb-/-, and Thrb2-/- received NaIO3 injection at P30. These mice were then analyzed for retinal function by electroretinography (ERG) and photoreceptor damage/cell death by biochemical and morphological approaches at 3 days post-NaIO3 injection, and for gene expression alterations at 1 day post-NaIO3 injection.
Treatment with antithyroid drug protected photoreceptors from oxidative damage and cell death induced by NaIO3, and preserved retinal function. The outer nuclear layer thickness and cone photoreceptor density were significantly increased in mice treated with antithyroid drug. Cone density was reduced by about 30% in mice after NaIO3 challenge. Deletion of TH receptor nearly completely abolished this reduction. The number of TUNEL-positive cells, the number of the DNA damage marker p-γH2AX-positive cells and 8-OHdG-positive cells, and Müller glia activation were significantly reduced in mice treated with antithyroid drug. NaIO3 treatment reduced scotopic and photopic ERG responses by about 40-50%, and treatment with antithyroid drug significantly preserved ERG responses. Gene expression analysis showed that the NaIO3-induced photoreceptor damage/cell death involves multiple mechanisms, including cellular oxidative stress responses, activation of necroptosis/apoptosis signaling, and inflammatory responses. Treatment with antithyroid drug abolished these cellular stress/death responses.
Suppression of TH signaling protects photoreceptors from oxidative damage and cell death induced by NaIO3 and may represent a strategy for photoreceptor protection in AMD.
This is a 2020 ARVO Annual Meeting abstract.
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