April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Intravitreal injection of IGFBP-3 restores normal insulin signaling in diabetic rat retina
Author Affiliations & Notes
  • Qiuhua Zhang
    Ophthalmology, Univ of Tennessee Hlth Sci Ctr, Memphis, TN
  • Youde Jiang
    Ophthalmology, Univ of Tennessee Hlth Sci Ctr, Memphis, TN
  • Jena J Steinle
    Ophthalmology, Univ of Tennessee Hlth Sci Ctr, Memphis, TN
    Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN
  • Footnotes
    Commercial Relationships Qiuhua Zhang, None; Youde Jiang, None; Jena Steinle, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5826. doi:
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    • Get Citation

      Qiuhua Zhang, Youde Jiang, Jena J Steinle; Intravitreal injection of IGFBP-3 restores normal insulin signaling in diabetic rat retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5826.

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

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Abstract

Purpose: To determine whether boosted expression of IGFBP-3 NB (a non-IGF-1 binding form of IGFBP-3) alone is sufficient to mimic the full actions of Compound 49b in protecting against diabetic retinopathy, as well as testing whether IGFBP-3 NB is linked to a restoration of normal insulin signal transduction.

Methods: Two months after initiation of streptozotocin-induced diabetes, rats received a single intravitreal injection of IGFBP-3 NB plasmid in the right eye. Four days after injection, electroretinogram (ERG) analyses were performed prior to sacrifice. Whole retinal lysates from control, diabetic, diabetic + control plasmid, and diabetic + IGFBP-3 NB were analyzed for IGFBP-3, TNFα, suppressor of cytokine signaling 3 (SOCS3), and insulin receptor signaling partners using Western blotting or ELISA.

Results: Data show that a single intraocular injection of IGFBP-3 NB in diabetic animals significantly reduced TNFα levels, concomitant with reductions in IRS-1Ser307, SOCS3, and pro-apoptotic markers, while restoring insulin receptor phosphorylation and increasing anti-apoptotic marker levels.

Conclusions: Our findings establish IGFBP-3 as a pivotal regulator of the insulin receptor/ TNFα pathway and a potential therapeutic target for diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 426 apoptosis/cell death • 715 signal transduction: pharmacology/physiology  
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