May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Macugen Induces Relocation of Tight Junction Proteins ZO-1 and Occludin After Treatment of iBREC With VEGF165
Author Affiliations & Notes
  • G. E. Lang
    Ophthalmology, University of Ulm, Ulm, Germany
  • G. K. Lang
    Ophthalmology, University of Ulm, Ulm, Germany
  • H. L. Deissler
    Ophthalmology, University of Ulm, Ulm, Germany
  • Footnotes
    Commercial Relationships G.E. Lang, research funding, F; G.K. Lang, research funding, F; H.L. Deissler, research funding, F.
  • Footnotes
    Support Grant by Pfizer Pharm GmbH, Medical Affairs Ophthalmics
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1357. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      G. E. Lang, G. K. Lang, H. L. Deissler; Macugen Induces Relocation of Tight Junction Proteins ZO-1 and Occludin After Treatment of iBREC With VEGF165. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1357. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose:: VEGF signalling is deregulated in diabetic retinopathy (DR) and is therefore a promising target for therapeutical intervention. Modified RNA-oligonucleotides (VEGF-aptamers) which inhibit the interaction of VEGF with its receptors are currently used to treat AMD. Tight junction proteins ZO-1 and occludin, usually detected in the plasma membrane of microvascular endothelial cells of the retina (REC), are relocated to the cytoplasm after treatment with VEGF165 likely leading to the breakdown of the blood-retina barrier. We therefore studied whether the VEGF aptamer Macugen (Pegaptanib) can revert VEGF induced delocalization of tight junction proteins in immortalized microvascular endothelial cells of the bovine retina (iBREC) in vitro.

Methods:: The protein composition of tight junctions in iBREC was studied by immunofluorescence staining in the presence and absence of VEGF165 and/or Macugen.

Results:: ZO-1, occludin and claudin-5 are strongly expressed at the plasma membrane in confluent iBREC, but are located in the cytoplasm in non-confluent cells. Low but specific expression at the plasma membrane of claudin-1 and claudin-3 was also detected. In the presence of 50 ng/ml VEGF165, ZO-1 and occludin were found in the cytoplasm after 1 to 2 days, whereas claudin-1, -3 or -5 were not influenced. However, after addition of 33 µg/ml Macugen for 24 h to VEGF165-treated iBREC, ZO-1 and occludin were again strongly expressed in the plasma membrane. In contrast, the plasma membrane localisation of the EC specific adherens junction protein VECadherin remained stable in the presence of VEGF165 and/or Macugen.

Conclusions:: Macugen reverted VEGF165-induced delocalization of tight junction proteins ZO-1 and occludin in iBREC, confirming an important role of tight junction proteins in the mechanism of Macugen’s action on endothelial cells.

Keywords: diabetic retinopathy • 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.

×