June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
TLR4 inhibits insulin signaling, leading to increased apoptosis in mouse retina
Author Affiliations & Notes
  • Youde Jiang
    Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Li Liu
    Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Elizabeth Curtiss
    Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Jena J Steinle
    Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Youde Jiang, None; Li Liu, None; Elizabeth Curtiss, None; Jena Steinle, None
  • Footnotes
    Support  R01EY022330
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4045. doi:
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    • Get Citation

      Youde Jiang, Li Liu, Elizabeth Curtiss, Jena J Steinle; TLR4 inhibits insulin signaling, leading to increased apoptosis in mouse retina
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):4045.

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

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Abstract

Purpose : We recently reported that Compound 49b, a b-adrenergic receptor agonist, could reduce toll-like receptor 4 (TLR4) levels and TNFalpha in retinal endothelial cells and diabetic mouse retina. Since we also have reported that Compound 49b restored normal insulin signaling in the retina, we hypothesized that TLR4 would inhibit insulin signaling, leading to apoptosis in the retina.

Methods : TLR4 floxed mice (B6 Cg-Tlr4tm1.1karp/J) and B6.FVB-Tg (cdh5-cre)7Mlia/J Cre mice purchased from Jackson lab were cross bred to produce endothelial cell-specific TLR4 knockout mice. TLR4 overexpressing mice were acquired from Dr. Fukuchi. Mice from each group were used at 3 months of age for Western blotting or ELISA for insulin receptor, insulin receptor substrate 1 (IRS-1), Akt, and cleaved caspase 3.

Results : Insulin receptor phosphorylation and Akt phosphorylation were increased in the retinal lysates fromTLR4 conditional knockout mice when compared to their floxed littermates. TLR4 overexpression significantly reduced insulin receptor and Akt phosphorylation in mouse retina. TLR4 floxed mice had significantly more phosphorylation of IRS-1Ser307 when compared to the conditional knockout mice. TLR4 overexpression increased IRS-1Ser307 phosphorylation in the mouse retina. Apoptosis was reduced in the retina from TLR4 conditional knockout mice, as well as in the littermates of the TLR4 overexpressing mice, when compared to TLR4 floxed and TLR4 overexpressing mice, respectively.

Conclusions : TLR4 signaling inhibits insulin signaling in the mouse retina, leading to increased apoptosis. Therapies designed to block TLR4 signaling may be protective to the retina.

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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