gms | German Medical Science

23rd Annual Meeting of the German Retina Society

German Retina Society

24.09. - 25.09.2010, Freiburg

Can genetically modified PEDF-secreting RPE cells substitute for anti-VEGFs for the treatment of exudative AMD?

Meeting Abstract

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  • Gabriele Thumann - Eye Clinic of the RWTH Aachen

German Retina Society. 23rd Annual Conference of the German Retina Society. Freiburg i. Br., 24.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10rg52

doi: 10.3205/10rg52, urn:nbn:de:0183-10rg523

This is the translated version of the article.
The original version can be found at: http://www.egms.de/de/meetings/rg2010/10rg52.shtml

Published: September 21, 2010

© 2010 Thumann.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: The intravitreal administration of VEGF inhibitors has resulted in significant recovery of vision in over 30% of patients with exudative AMD. In addition to the possible system side effects, the frequent, possibly life-long intravitreal injections are accompanied by significant ocular risks. To overcome the disadvantages of frequent anti-VEGF injections, we have transfected RPE cells with the gene for PEDF using non-viral protocols. Transplantation of these cells to the subretinal space will inhibit neovascularization and maintain a proper neurogenic microenvironment.

Methods: Using electroporation RPE cells were transfected with a plasmid encoding for PEDF. To evaluate transfection efficiency and protein expression stability, secreted rPEDF was identified by immunoblotting at various times. rPEDF was compared in vitro to bevacizumab for its ability to inhibit vascular endothelial cell chemotaxis, sprouting and induction of apoptosis of vascular endothelial cells. Genome stability of the transfected RPE cells was examined using real time PCR to analyze tumor and differentiation markers.

Results: Transfected RPE cells stable PEDF expression for at least 1.5 years and 50 passages, secreting at a rate of 32 ng PEDF/hour/100,000 cells. rPEDF inhibited in vitro endothelial cell proliferation, chemotaxis and sprouting and compared to bevacizumab the rPEDF was over 2000 times more potent. No significant change was evident in gene expression expression.

Conclusions: Genetic ex vivo modification of pigment epithelial cells to produce elevated levels of PEDF should improve the potential therapeutic treatment of AMD by transplantation of these cells to the subretinal space where it would inhibit neovascularization and improve RPE survival.