May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Src kinase inhibition reduces laser or VEGF induced retinal vascular permeability
Author Affiliations & Notes
  • E. Aguilar
    Cell Biology,
    The Scripps Research Institute, San Diego, CA
  • R.F. Gariano
    Cell Biology,
    The Scripps Research Institute, San Diego, CA
  • L. Scheppke
    Cell Biology,
    The Scripps Research Institute, San Diego, CA
  • S. Weiss
    Immunology,
    The Scripps Research Institute, San Diego, CA
  • D.A. Cheresh
    Immunology,
    The Scripps Research Institute, San Diego, CA
  • M. Friedlander
    Cell Biology,
    The Scripps Research Institute, San Diego, CA
  • Footnotes
    Commercial Relationships  E. Aguilar, None; R.F. Gariano, None; L. Scheppke, None; S. Weiss, None; D.A. Cheresh, None; M. Friedlander, None.
  • Footnotes
    Support  R01 EY11254 (MF), Skaggs Clinical Scholar Program (RFG)
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 499. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      E. Aguilar, R.F. Gariano, L. Scheppke, S. Weiss, D.A. Cheresh, M. Friedlander; Src kinase inhibition reduces laser or VEGF induced retinal vascular permeability . Invest. Ophthalmol. Vis. Sci. 2004;45(13):499.

      Download citation file:


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

      ×
  • Supplements
Abstract

Abstract: : Purpose: Members of the family of src kinases mediate vascular permeability increases in non–ocular tissues due to ischemia or to exogenous administration of Vascular Endothelial Growth Factor (VEGF). We examined whether src kinase vascular mediated pathways regulate vascular permeability in the retina. Methods:Retinal vascular permeability in adult mice was determined qualitatively by confocal fluorescent microscopic inspection of retinal wholemounts following perfusion with fluorescein–dextran, and quantitatively by measurement of tissue concentrations of intravenously injected Evans Blue dye. Permeability was assessed 4–5 hours after intravitreal injection of VEGF (65 ng/.3 µl) or buffer, or three days after laser–induced occlusion of retinal arteries and veins at the optic nerve head. Inhibition of src kinase was achieved by systemic injection of either 4–amino–5–(4–methylphenyl)–7–(t–butyl) pyrazolo[3,4–d]pyrimidine (PP1; 1.5mg/kg ip) or N–methylpiperazine (NMP; 5mg/kg iv). Results: In response to intravitreal VEGF injection, vascular leakage was observed in wholemounted retinas by perivascular dextran extravasation. Quantification of this effect demonstrated that Evans blue dye levels increased approximately 2–3 fold in VEGF–treated eyes; this increase was abolished by systemic administration of the src kinase inhibitors PP1 or NMP (100% reversal of VEGF effect, p<0.05). In retinas that underwent laser vaso–occlusion, retinal hypoperfusion and diffuse and focal dextran extravasation were detected. Evans blue accumulation increased approximately 3–4 fold in laser–treated eyes compared to untreated fellow eyes; this increase was markedly attenuated by treatment with PP1 (45% reduction, p<0.05), and was nearly eliminated by NMP (87% reversal, p<0.05). Src kinase inhibitors alone did not significantly alter retinal permeability in the absence of VEGF or laser treatment. Conclusions: Src kinases are key mediators of retinal vascular permeability. Inhibition of src kinase activities eliminates retinal hyperpermeability due to VEGF administration and markedly reduces vascular leakage in an in vivo model of ischemic retinopathy. These data complement previously reported roles for src kinases in the control of non–retinal microvascular permeability, and support further investigations of src kinase inhibition in the management of blinding eye diseases characterized by excessive retinal vascular leakage.

Keywords: retina • growth factors/growth factor receptors • retinal neovascularization 
×
×

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.

×