June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Retinal neuronal SOCS3 governs EGF signaling and neovascular growth
Author Affiliations & Notes
  • Ye Sun
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Meihua Ju
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Andreas Stahl
    University Eye Hospital Freiburg Killianstrasse 5, Freibury, Germany
  • Lucy Evans
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Katherine Tian
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Nicholas Saba
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Thomas Fredrick
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Peyton Morss
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Jing Chen
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Lois E H Smith
    Ophthalmology, Harvard Med School/Boston Children's Hospital, Boston, MA
  • Footnotes
    Commercial Relationships Ye Sun, None; Meihua Ju, None; Andreas Stahl, None; Lucy Evans, None; Katherine Tian, None; Nicholas Saba, None; Thomas Fredrick, None; Peyton Morss, None; Jing Chen, None; Lois Smith, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2049. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Ye Sun, Meihua Ju, Andreas Stahl, Lucy Evans, Katherine Tian, Nicholas Saba, Thomas Fredrick, Peyton Morss, Jing Chen, Lois E H Smith; Retinal neuronal SOCS3 governs EGF signaling and neovascular growth. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2049.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: Neurovascular interactions are important in the maintenance of normal function in the nervous system, and defects in this relationship often lead to various forms of disease. Accumulating evidence suggests that crosstalk between vasculature and the retinal neuroglia, photoreceptors and other neural cells in diabetes might contribute to the pathogenesis of diabetic retinopa­thy. However, the molecular mechanisms regulating neurovascular interaction in pathologic retinal angiogenesis are not well known. We identified a novel mechanism by which neurons govern neovascularization in retinopathy through neuronal/glial SOCS3.

Methods: We generated conditional knockout of suppressor of cytokine signaling 3 (SOCS3) inneurons and glias by crossing mice expressing the Cre recombinase transgene under the control of the nestin (Nes) promoter with mice carrying Socs3/loxP. Pathologic retinal angiogenesis was studied using a mouse oxygen-induced retinopathy (OIR) model, in which neonatal pups are exposed to 75% oxygen from postnatal day (P) 7 to 12. Laser capture microdissection, RNA Isolation, quantitative RT-PCR and western blot were performed to analyse gene expressions. Immunohistochemistry and confocal imaging were performed to demonstrate protein localization and cell type identification. Immunoblot was used to demonstrate protein phosphorylation.

Results: Conditional Socs3 knockout mice (Socs3Nes-ko) subjected to OIR had significantly increased levels of pathologic retinal neovascularization compared with littermate controls (Socs3flox/flox) at P17 (Socs3Nes-ko, 11.65%±0.65%, n=27; Socs3flox/flox, 8.30%±0.57%, n=10; P=0.002). The vaso-obliterated retinal area was significantly reduced (p=0.004) in Socs3Nes-ko (13.65%±1%, n=27) compared with Socs3flox/flox mice (16.8%±0.49%, n=10). In neuronal/glial Socs3 deficient retinas Vegfa expression was significantly increased. Lack of neuronal/glial SOCS3 does not affect HIF-1α level, but resulted in high level of phospho-STAT3, elevated Vegf receptors Flt1 and Flk1 expression, and activated phospho-ERK.

Conclusions: In summary, neuronal/glial SOCS3 suppresses pathologic endothelial activation through inhibiting STAT3 activation mediated VEGF-induced ERK activation. Together this study identifies neuronal/glial SOCS3 as a novel regulator of neurovascular interaction and pathologic retinal angiogenesis through titration of VEGF signaling.

×
×

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.

×