April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Sustained Intraocular Production of Placental Growth Factor (pgf), Using Ciliary Muscle Electrotransfer: A Model for Early Diabetic Retinopathy Changes?
Author Affiliations & Notes
  • L. Kowalczuk
    Physiopathology of Ocular Diseases: Therapeutic innovations, CRC UMRS 872 Team 17, Université Pierre et Marie Curie, Université Paris Descartes, F-75006 Paris, France
  • E. Touchard
    Physiopathology of Ocular Diseases: Therapeutic innovations, CRC UMRS 872 Team 17, Université Pierre et Marie Curie, Université Paris Descartes, F-75006 Paris, France
  • C. Goumeaux
    Physiopathology of Ocular Diseases: Therapeutic innovations, CRC UMRS 872 Team 17, Université Pierre et Marie Curie, Université Paris Descartes, F-75006 Paris, France
  • L. Jonet
    Physiopathology of Ocular Diseases: Therapeutic innovations, CRC UMRS 872 Team 17, Université Pierre et Marie Curie, Université Paris Descartes, F-75006 Paris, France
  • P. Bigey
    Chemical and Genetic Pharmacology Laboratory, ENSCP, INSERM U640, CNRS UMR8151, Faculté de Pharmacie, F-75005 Paris, France
  • J.-C. Jeanny
    Physiopathology of Ocular Diseases: Therapeutic innovations, CRC UMRS 872 Team 17, Université Pierre et Marie Curie, Université Paris Descartes, F-75006 Paris, France
  • F. Behar-Cohen
    Physiopathology of Ocular Diseases: Therapeutic innovations, CRC UMRS 872 Team 17, Université Pierre et Marie Curie, Université Paris Descartes, F-75006 Paris, France
    Department of Ophthalmology, Hôtel-Dieu, F-75004 Paris, France
  • Footnotes
    Commercial Relationships  L. Kowalczuk, None; E. Touchard, None; C. Goumeaux, None; L. Jonet, None; P. Bigey, None; J.-C. Jeanny, None; F. Behar-Cohen, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5906. doi:
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      L. Kowalczuk, E. Touchard, C. Goumeaux, L. Jonet, P. Bigey, J.-C. Jeanny, F. Behar-Cohen; Sustained Intraocular Production of Placental Growth Factor (pgf), Using Ciliary Muscle Electrotransfer: A Model for Early Diabetic Retinopathy Changes?. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5906.

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

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Abstract

Purpose: : The purpose of this study was to evaluate clinical and histopathological ocular changes induced by sustained PGF over-expression in rat eyes using electrotransfer (ET).

Methods: : Ciliary muscle injection of pVAX2-rPGF (30µg) combined with ET (200V/cm) was performed in pigmented and non-pigmented rat eyes. Control eyes received ciliary muscle ET of saline. Clinical signs induced by PGF secretion in ocular media were followed up until three months after ET by slit lamp examination and by fluorescein angiography. Ciliary bodies were dissected and used for the evaluation of the PGF mRNA levels. The effect of PGF secretion on ocular structures was evaluated by semi-thin sections analysis and by immunohistochemistry for PGF, GFAP, alpha-SMA, Von Willbrand. Retinal vasculature was analyzed by lectin and GFAP staining on flat-mounted retina.

Results: : Compared with control eyes, PGF expression was significantly increased in the ciliary muscle eyes receiving pVAX2-rPGF ET as confirmed by PCR and immunohistochemitry. Rat PGF secretion induced retinal pigmented epithelial barrier breakdown with subsequent retinal edema, together with retinal vessel abnormalities (diffusion, diffusing microaneurysms, irregularities...). Histological analysis showed that associated to the retinal vessel abnormalities, pre retinal GFAP positive membranes could be observed.

Conclusions: : Over expression of PGF induces retinal abnormalities resembling to diabetic retinopathy. These observations confirm that PGF/ VEGFR1 may be potential targets for the treatment of diabetic retinopathy.

Keywords: gene transfer/gene therapy • growth factors/growth factor receptors • diabetic retinopathy 
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