May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Regulation of Igf-1 Receptor Signaling by Sympathetic Neurotransmission
Author Affiliations & Notes
  • S. Panjala
    Ophthalmology, Univ of Tennessee Hlth Sci Cntr, Memphis, Tennessee
  • S. Thomas
    Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania
  • J. Steinle
    Ophthalmology, Univ of Tennessee Hlth Sci Cntr, Memphis, Tennessee
  • Footnotes
    Commercial Relationships  S. Panjala, None; S. Thomas, None; J. Steinle, None.
  • Footnotes
    Support  JDRF 2-2006-114; Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4907. doi:https://doi.org/
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    • Get Citation

      S. Panjala, S. Thomas, J. Steinle; Regulation of Igf-1 Receptor Signaling by Sympathetic Neurotransmission. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4907. doi: https://doi.org/.

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

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Abstract

Purpose: : To determine whether IGF-1 signaling alters rates of apoptosis in dopamine beta hydroxylase (DBH KO) knockout mice.

Methods: : Retinal lysates from knockout mice for dopamine beta hydroxylase [DBH (-/-)] and their heterozygote littermates [DBH (+/-)] were used to examine the role of norepinephrine (NE) in the regulation IGF-1 signaling and apoptosis in the retina. Western blot analysis was done for protein levels of IGF-1 receptor, phosphorylated IGF-1 receptor, phosphorylated IRS-1 on serine 636/639, total IRS-1, phosphorylated IRS-2 on serine 731, total IRS-2, phosphorylated Akt on serine 473 and total Akt. ELISA was done to determine caspase-3 levels in the retina.

Results: : IGF-1 receptor phosphorylation is significantly decreased in DBH KO mice as compared to their heterozygote littermates (P<0.05 vs. WT). Phosphorylation of IRS-1 protein was increased in KO mice (P<0.05 vs. WT). Conversely, IRS-2 protein phosphorylation was significantly decreased in KO mice when compared with WT mice (P<0.05 vs. WT). Akt protein phosphorylation is also reduced in the KO mice, leading to increased cleaved caspase 3 levels.

Conclusions: : Our results suggest that IGF-1 receptor signaling is reduced in mice with dysfunctional sympathetic neurotransmission. The data also indicate that IGF-1 signaling occurs primarily through IRS-2 rather than IRS-1. The reduction in Akt phosphorylation, likely through reduced IGF-1 receptor signaling, could explain the increase in cleaved caspase 3. These results suggest that alterations in sympathetic neurotransmission modulate IGF-1 signaling, which directly or indirectly regulates apoptosis in the retina. These results suggest that restoration of sympathetic neurotransmission may be a new target for therapeutic intervention to inhibit the early phases of diabetic retinopathy.

Keywords: diabetic retinopathy • retinal culture • signal transduction 
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