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Fan Yang, Hongwei Ma, Michael Butler, Xi-Qin Ding; Impaired Rod and Cone Photoreceptor Function in Mice Lacking Type II Iodothyronine Deiodinase. Invest. Ophthalmol. Vis. Sci. 2017;58(8):345.
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© ARVO (1962-2015); The Authors (2016-present)
Thyroid hormone (TH) signaling regulates numerous physiological functions, including cell growth, differentiation, and metabolic homeostasis. In the retina, TH signaling is known to regulate cone opsin expression and affect cone viability. Although TH levels in the circulation are fairly stable, the intracellular TH signaling is regulated by the type II iodothyronine deiodinase (DIO2) which converts the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3). This work investigates the necessity of DIO2 for the retinal function and survival using DIO2-deficient mice.
The retinal function in Dio2-/- mice was measured by electroretinogram (ERG). Rod and cone survival was evaluated by analyzing the thickness of the outer nuclear layer (ONL) and cone density. The expression levels of the rod and cone phototransduction components were examined by q-RT-PCR and immunoblotting. To further clarify the role of TH signaling, we conducted a T3 supplementation experiment (0.1µg/ml and 0.3µg/ml in drinking water) in Dio2-/- mice.
The scotopic and photopic ERG responses in 1-month-old and 5-month-old Dio2-/- mice were reduced by about 50% compared to wild-type (WT) mice. No differences in ONL thickness and cone density were observed between Dio2-/- and WT mice. Although we did not observe a reduction in cone opsin expression, the expression levels of G protein subunit alpha transducin 2 (GNAT2) and cone arrestin (CAR) were significantly reduced in Dio2-/- mice compared to WT. However, we did not detect any alteration in the expression levels of the rod phototransduction proteins, including rhodopsin, rod transducin and rod arrestin. The ERG responses and the expression levels of GNAT2 and CAR were rescued in Dio2-/- mice after T3 treatment.
DIO2-deficient mice show an impaired retinal function without a significant loss of photoreceptors. The phenotypes were rescued by supplementation of T3, indicating a TH-dependent retinal functionality and the necessity of DIO2 for retinal functional development. The reduced expression levels of the cone phototransduction proteins may explain the cone defects in Dio2-/- mice. However, how rod function is affected remains to be elucidated.
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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