July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
RNAseq Analysis to Understand the Cellular Mechanisms Involved in Thyroid
Hormone Signaling Suppression-induced Cone Protection
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
  • Willard M. Freeman
    Department of Physiology, 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; Willard Freeman, None; Xi-Qin Ding, None
  • Footnotes
    Support  This work was supported by grants from the National Eye Institute (P30EY021725 and R21EY024583), the Foundation Fighting Blindness, and the Knights Templar Eye Foundation.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 974. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Hongwei Ma, Fan Yang, Willard M. Freeman, Xi-Qin Ding; RNAseq Analysis to Understand the Cellular Mechanisms Involved in Thyroid
      Hormone Signaling Suppression-induced Cone Protection. Invest. Ophthalmol. Vis. Sci. 2018;59(9):974.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Suppressing thyroid hormone (TH) signaling protects cones in retinal degeneration model mice, including the leber congenital amaurosis (LCA) model Rpe65-/- mice. Using RNAseq, this work profiles the retinal gene expression alterations in order to explore the cellular mechanisms underlying how TH signaling suppression protects cones.

Methods : Cone-dominant Rpe65-/-/Nrl-/- and Nrl-/- mouse lines were used. Rpe65-/-/Nrl-/- mice were treated with anti-thyroid drug (methimazole and sodium perchlorate monohydrate) or vehicle between postnatal (P) day 2 and P15. Retinas were collected at the end of the treatment for total RNA and cDNA library preparation/quantification. RNAseq was conducted using a NextSeq V2 High PE75 Kit (Illumina) and Ingenuity Pathway Analysis. Selected genes were validated by qRT-PCR.

Results : We found 1092 and 1584 genes altered in Rpe65-/-/Nrl-/- mice relative to Nrl-/- mice, and in Rpe65-/-/Nrl-/- mice treated with anti-thyroid drugs relative to vehicle-treated controls, respectively. Among 387 genes shared in both comparisons, 111 genes were found to be involved in cell death and survival, and 94% of these genes were oppositely altered in the two comparisons, suggesting an effect of TH signaling suppression on the cellular death/survival regulations. The top upstream regulators identified included tumor necrosis factor (TNF) and lipopolysaccharide (LPS)-mediated cellular necroptosis and inflammation pathways, showing activation in Rpe65-/-/Nrl-/- mice and inhibition after treatment with anti-thyroid drug. Ingenuity Pathways Analysis also identified several top molecular and cellular functions, including cellular morphology, cell death/survival, molecular transport, cellular movement, cellular growth and proliferation, and cellular development in Rpe65-/-/Nrl-/- mice.

Conclusions : RNAseq analysis shows TH signaling suppression significantly affects the cellular death/survival pathways and suggests a potential role of necroptosis/inflammation-associated cellular death/survival pathways in the observed cone protection.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×