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Hongwei Ma, Michael Robert Butler, Josh Belcher, T Michael Redmond, Thomas S. Scanlan, Xi-Qin Ding; Inhibition of Thyroid Hormone Receptor Signaling Protects Cones in Mouse Model of Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5474.
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Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and apoptosis. In the retina, TH signaling plays a central role in cone opsin expression and patterning. We previously showed that suppressing TH signaling by anti-thyroid treatment preserves cones in mouse models of retinal degeneration. This work investigates whether inhibition of thyroid hormone receptors (TRs) affects cone viability in retinal degeneration model mice.
The cone precursor Weri RB-1 cell line was used to determine the antagonistic activity of the TR antagonists, NH3 and 1-850. Expression levels of M-opsin, S-opsin, and TRβ2 in Weri cells following T3 treatment in the presence and absence of TR antagonists were analyzed by quantitative RT-PCR. The cone degeneration mouse model, Rpe65-/-, was used to determine whether treatment with TR antagonists protects cones. NH3 or 1-850 or vehicle was delivered to the eye by intravitreal injection at postnatal day 5 (P5), and retinas and eyes were collected on P24. 1-850 or vehicle was also injected intraperitoneally daily from P5 to P29, and retinas and eyes were collected on P30. Cone survival was evaluated by examining cone density on retinal whole mounts and retinal sections by immunohistochemical approaches.
Treatment with T3 increased M-opsin expression and decreased S-opsin expression in Weri cells. The effects of T3 treatment were inhibited by NH3 and 1-850 in a dose-dependent pattern. Cone density in Rpe65-/- mice increased by about 35% following NH3 and 1-850 treatment.
We show that treatment with TR antagonists systemically or ocularly improved cone survival in Rpe65-/- mice. Our findings suggest that inhibition of TR signaling locally in the retina may represent a novel strategy for retinal degeneration management.
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