May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Type 3 Deiodinase, a Thyroid-Hormone Inactivating Enzyme, Regulates Maturation and Survival of Cone Photoreceptors
Author Affiliations & Notes
  • A. L. Lyubarsky
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • L. Ng
    Clinical Endocrinology, NIH, NIDDK, Bethesda, Maryland
  • M. Ma
    Clinical Endocrinology, NIH, NIDDK, Bethesda, Maryland
  • M. Srinvas
    Human Genetics, Mount Sinai School of Medicine, New York, New York
  • V. A. Galton
    Physiology, Dartmouth Medical School, Lebanon, New Hampshire
  • D. S. Germain
    Physiology, Dartmouth Medical School, Lebanon, New Hampshire
  • E. N. Pugh, Jr.
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania
  • A. Hernandez
    Physiology, Dartmouth Medical School, Lebanon, New Hampshire
  • D. Forrest
    Clinical Endocrinology, NIH, NIDDK, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  A.L. Lyubarsky, None; L. Ng, None; M. Ma, None; M. Srinvas, None; V.A. Galton, None; D.S. Germain, None; E.N. Pugh, None; A. Hernandez, None; D. Forrest, None.
  • Footnotes
    Support  NIH-EY2660, NIH NIDDK Intramural Program, NIH HD-09020, NIH DK-42271, Hirschl Award
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1259. doi:https://doi.org/
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      A. L. Lyubarsky, L. Ng, M. Ma, M. Srinvas, V. A. Galton, D. S. Germain, E. N. Pugh, Jr., A. Hernandez, D. Forrest; Type 3 Deiodinase, a Thyroid-Hormone Inactivating Enzyme, Regulates Maturation and Survival of Cone Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1259. doi: https://doi.org/.

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

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Abstract

Purpose: : To investigate the role of Type 3 deiodinase (D3) in the development of the mouse retina.

Methods: : We studied retinal function in (1) mice that have D3, a thyroid hormone-inactivating enzyme encoded by Dio3, inactivated by deletion of the Dio3 gene (Dio3-/-); (2) mice with both the D3 and thyroid hormone receptor, TRβ2 deleted (Dio3-/- Thrb2-/-).

Results: : In Dio3-/- animals, cones are formed, but ~80% of both M and S sub-types are lost through increased rates of neonatal cell death, though rod photoreceptors remain morphologically intact. ERG studies on these animals revealed a drastic reduction in amplitude of the cone b-wave from 223±57 µV in wild type (WT) to 45±7 µV in Dio3-/- mice. These results are consistent with ~80% cone loss observed in morphological studies. Rod-driven ERG components, both the a- and b-wave, were only moderately (by ~25%) though statistically significantly diminished in the Dio3-/- animals. Elimination of a thyroid hormone receptor, TRβ2, in addition to D3 in Dio3-/- Thrb2-/- mice resulted in rescue of cones. The amplitude of the saturating cone b-wave in these animals was similar to that in the WT mice. The spectral sensitivity of cone ERG in the Dio3-/- Thrb2-/- was characterized with enhanced sensitivity to the near UV (365 nm) light and dramatic decrease in sensitivity to illumination in the M pigment band, similar to Thrb2-/- mice. The Dio3-/- Thrb2-/- mice also exhibited a ~25% lower amplitudes of the saturating rod a-wave.

Conclusions: : D3, a thyroid-hormone inactivating enzyme, regulates maturation and survival of cone photoreceptors. In absence of the D3 80% of cones die within two days of birth. The cone loss in Dio3-/- mice is reversed upon deletion of TRβ2 receptor for the hormone; the overwhelming majority of cones then acquires a pure S opsin identity. Thus, decisions in cone development are balanced by thyroid hormone: D3 normally limits the level of hormonal stimulation to permit opsin patterning whereas excessive stimulation in Dio3-/- mice selectively eliminates cones.

Keywords: electroretinography: non-clinical • photoreceptors • development 
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