April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Gene Therapy of a CNV Rodent Model Using Non-virally Stably Transfected RPE Cells with the PEDF Gene
Yassin Djalali-Talab; Olga Kazanskaya; Sandra Johnen; Antonis Koutsonas; Narendra Armogan; Peter Walter; Gabriele Thumann
Author Affiliations & Notes
  • Yassin Djalali-Talab
    Department of Ophthalmology, RWTH Aachen University, Aachen, Germany
  • Olga Kazanskaya
    Department of Ophthalmology, RWTH Aachen University, Aachen, Germany
  • Sandra Johnen
    Department of Ophthalmology, RWTH Aachen University, Aachen, Germany
  • Antonis Koutsonas
    Department of Ophthalmology, RWTH Aachen University, Aachen, Germany
  • Narendra Armogan
    Department of Ophthalmology and Vision Sciences, University of Toronto, Ontario, Canada
  • Peter Walter
    Department of Ophthalmology, RWTH Aachen University, Aachen, Germany
  • Gabriele Thumann
    Department of Ophthalmology, RWTH Aachen University, Aachen, Germany
  • Footnotes
    Commercial Relationships  Yassin Djalali-Talab, None; Olga Kazanskaya, None; Sandra Johnen, None; Antonis Koutsonas, None; Narendra Armogan, None; Peter Walter, None; Gabriele Thumann, None
  • Footnotes
    Support  Supported by a grant from the IZKF Aachen (Interdisciplinary Centre for Clinical Research within the faculty of Medicine at RWTH Aachen University)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4380. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      Gene Therapy of a CNV Rodent Model Using Non-virally Stably Transfected RPE Cells with the PEDF Gene
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      Yassin Djalali-Talab, Olga Kazanskaya, Sandra Johnen, Antonis Koutsonas, Narendra Armogan, Peter Walter, Gabriele Thumann; Gene Therapy of a CNV Rodent Model Using Non-virally Stably Transfected RPE Cells with the PEDF Gene. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4380.

      Download citation file:

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

      ×
    • Get Permissions
  • Supplements
Abstract

Purpose: : Choroidal neovascularization (CNV) is the leading cause of vision loss in AMD. Since PEDF is a potent inhibitor of angiogenesis as well as a neuroprotective agent, it would be expected that transplantation of pigment cells genetically modified to secrete high levels of PEDF could be used to treat neovascular AMD. This study evaluates the effect of transplantation of PEDF-transfected homologous RPE cells into the subretinal space of rats after laser-induced CNV.

Methods: : Inhibition of migration and tube formation by human umbilical vein endothelial cells (HUVECs) was employed to quantify anti-angiogenic activity of rPEDF produced by PEDF-transfected homologous RPE cells. The effect of rPEDF and transplanted non-virally mediated PEDF-transfected cells in vivo was examined on CNV lesions generated by laser photocoagulation of the fundus in 24 Long Evans rats. Immediately after laser treatment, 1 µg of rPEDF or 2x104cells expressing human PEDF at 100 ng/day or control protein (Venus, yellow fluorescent mutant of GFP) were injected into the subretinal space. Extent of CNV was evaluated by isolectin B4 staining of choroid-RPE-flat mounts at 8 weeks and by fluorescein angiography (FAG) on day 7 and at 8 weeks. Distribution and state of injected cells was evaluated by immunostaining with anti-5 His antibody.

Results: : At a concentration of 100 ng/ml rPEDF inhibited HUVEC migration by 76% and tube formation by 66%. In this series of rats 1 µg of rPEDF reduced cumulative CNV area by 60% and 2x104RPE cells overexpressing PEDF reduced cumulative CNV area by 50%. FAG analysis indicated that 1 µg rPEDF and PEDF-overexpressing RPE cells reduced the CNV leakage area by 42% and by 50%, respectively.

Conclusions: : The results of this study show that as little as 1 µg of rPEDF and as few as 20,000 RPE cells transfected with the PEDF gene and secreting PEDF at a concentration of 100 ng/day are able to control the development of neovscularization in a rat model of CNV. These studies indicate that pigment cells transfected with the PEDF gene would be effective to inhibit the neovascularisation in neovascular AMD and other neovascular diseases of the retina.

Keywords: age-related macular degeneration • gene transfer/gene therapy • choroid: neovascularization 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
×
×

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.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept