June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Targeting Thyroid Hormone Signaling to Protect Retinal Pigment Epithelium from Oxidative Stress
Author Affiliations & Notes
  • Hongwei Ma
    The Department of Cell Biology, Univ of Oklahoma Health Sci Ctr, Oklahoma City, Oklahoma, United States
  • Fan Yang
    The Department of Cell Biology, Univ of Oklahoma Health Sci Ctr, Oklahoma City, Oklahoma, United States
  • Michael Butler
    The Department of Cell Biology, Univ of Oklahoma Health Sci Ctr, Oklahoma City, Oklahoma, United States
  • Xi-Qin Ding
    The Department of Cell Biology, Univ of Oklahoma Health Sci Ctr, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Hongwei Ma, None; Fan Yang, None; Michael Butler, None; Xi-Qin Ding, None
  • Footnotes
    Support  This work was supported by grants from the National Eye Institute (P30EY021725, R01EY019490, and R21EY024583), the Foundation Fighting Blindness, and the Knights Templar Eye Foundation.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1606. doi:
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    • Get Citation

      Hongwei Ma, Fan Yang, Michael Butler, Xi-Qin Ding; Targeting Thyroid Hormone Signaling to Protect Retinal Pigment Epithelium from Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1606.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The retinal pigment epithelium (RPE) plays a critical role in visual function, and RPE oxidative damage/dystrophy is at the core of age-related macular degeneration (AMD). Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent population-based cohort studies showed that higher free serum TH values were associated with increased risk of AMD, implying that TH signaling may be involved in the pathogenesis of AMD. This work investigates the effects of TH signaling manipulation on RPE viability under normal and stressed conditions.

Methods : The expression levels of TH receptors in the mouse RPE were analyzed by qRT-PCR. The effects of TH signaling suppression was evaluated by anti-thyroid drug treatment. C57BL/6 mice received methimazole (0.05% in drinking water) and sodium perchlorate monohydrate (1% in drinking water) or vehicle for 12 days, starting at postnatal day 20 (P20), and received a bolus injection of sodium iodate (NaIO3, 30 mg/kg, i.p.) or vehicle at P30. Forty-eight hours after treatment with NaIO3, mice were evaluated for RPE morphology by phalloidin staining on RPE flat-mounts, and for expression of the oxidative stress genes in the RPE by qRT-PCR. We also examined the effects of TH signaling stimulation. C57BL/6 mice received triiodothyronine (T3) treatment (0.1 µg/g/day, s.c.) for 5 days, starting at P10, and were then analyzed for expression of the oxidative stress genes in the RPE.

Results : Expression levels of all three types of the TH receptors (Thrα1, Thrβ1, and Thrβ2) in the RPE were 3-5 folds higher than that in retinas. The RPE in mice treated with NaIO3 showed severe necrosis/apoptosis and enhanced expression of the oxidative stress genes, compared with vehicle-treated controls. Treatment with anti-thyroid drug significantly improved RPE morphology, reduced cell loss, and reduced expression of the oxidative stress genes in mice that have been treated with NaIO3. In addition, treatment with T3 significantly increased expression levels of the oxidative stress genes in the RPE.

Conclusions :
This work shows that suppressing TH signaling with anti-thyroid drug improves RPE morphology and survival in mice challenged with oxidative stress. Our findings are in line with the clinical findings, and suggest that suppressing TH signaling may represent a strategy for RPE protection in AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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