April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Vascular Permeability and Apoptosis Are Separable Processes in Ischemia-Reperfusion Retinopathy: Effects of Preconditioning and Bevacizumab
Author Affiliations & Notes
  • S. F. Abcouwer
    Surgery, Cellular & Molecular Physiology, and Opthalmology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • C.-M. Lin
    Cellular & Molecular Physiology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • E. B. Wolpert
    Cellular & Molecular Physiology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • S. Shanmugam
    Cellular & Molecular Physiology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • W. M. Freeman
    Pharmacology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • E. W. Schaefer
    Public Health Science,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • A. J. Barber
    Ophthalmology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • T. W. Gardner
    Ophthalmology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • D. A. Antonetti
    Cellular & Molecular Physiology, and Ophthalmology,
    Penn State University College of Medicine, Hershey, Pennsylvania
  • Footnotes
    Commercial Relationships  S.F. Abcouwer, None; C.-M. Lin, None; E.B. Wolpert, None; S. Shanmugam, None; W.M. Freeman, None; E.W. Schaefer, None; A.J. Barber, None; T.W. Gardner, None; D.A. Antonetti, None.
  • Footnotes
    Support  Supported by the JDRF (Juvenile Diabetes Research Foundation) Diabetic Retinopathy Center at Penn State
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3657. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      S. F. Abcouwer, C.-M. Lin, E. B. Wolpert, S. Shanmugam, W. M. Freeman, E. W. Schaefer, A. J. Barber, T. W. Gardner, D. A. Antonetti; Vascular Permeability and Apoptosis Are Separable Processes in Ischemia-Reperfusion Retinopathy: Effects of Preconditioning and Bevacizumab. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3657.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : This study compared the effects of ischemic preconditioning (IPC) and targeting vascular endothelial growth factor (VEGF) on retinal apoptosis, vascular permeability and mRNA biomarker expression in a model of transient retinal ischemia followed by reperfusion (IR).

Methods: : Sprague-Dawley rats were subjected to 45 minutes of retinal ischemia through elevated intraocular pressure, followed by reperfusion for various times up to 48 h. VEGF expression was quantified by Western blotting. IPC was induced by 10 min of ischemia 24 h prior to IR. Intravitreal injection of bevacizumab (Avastin®) 48 h prior to IR was used to block retinal VEGF function. Retinal neuronal apoptosis was quantified by measuring caspase-3 (DEVDase) activity and DNA fragmentation. Vascular permeability was quantified by measuring the accumulation of Evan’s Blue dye in retinal tissue. A set of 35 mRNA biomarkers with IR-responsive expression was identified and utilized to examine treatment responses.

Results: : IR caused significant increases in retinal VEGF protein expression, cell apoptosis, and Evan’s blue dye accumulation that persisted for at least 48 h. IPC abrogated apoptosis, but did not significantly affect Evan’s blue accumulation. Bevacizumab effectively inhibited accumulation of Evan’s blue, but did not affect apoptosis. IPC altered the IR responses of 15 mRNAs, while bevacizumab affected the IR responses of only 2 of the mRNA biomarkers.

Conclusions: : IR provides an acute model of ischemic retinopathy that includes neurodegeneration and VEGF-dependent vascular permeability. The distinct effects of IPC and bevacizumab demonstrate that the apoptotic and vascular pathologies may require separate therapeutic interventions. Blocking VEGF did not induce apoptosis or exacerbate the ischemic effect on neurodegeneration, supporting the use of bevacizumab to treat vascular permeability in retinal disease.

Keywords: ischemia • retina • vascular endothelial growth factor 
×
×

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.

×