Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
Our findings establish IGFBP-3 as a pivotal regulator of the insulin receptor/ TNFα pathway and a potential therapeutic target for diabetic retinopathy.
This PDF is available to Subscribers Only