title: Placental growth factor contributes to micro-vascular abnormalization and blood-retinal barrier breakdown in diabetic retinopathy.
abstract: OBJECTIVE
  There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1).
  
  
  METHODS
  pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis.
  
  
  RESULTS
  After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation.
  
  
  CONCLUSIONS
  This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease.
authors.affiliation: Institut National pour la Santé Et la Recherche Médicale U872, Physiopathology of ocular diseases: Therapeutic innovations, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Kowalczuk
authors.forename: Elodie
authors.initials: E
authors.lastname: Touchard
authors.forename: Samy
authors.initials: S
authors.lastname: Omri
authors.forename: Laurent
authors.initials: L
authors.lastname: Jonet
authors.forename: Christophe
authors.initials: C
authors.lastname: Klein
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Valamanes
authors.forename: Marianne
authors.initials: M
authors.lastname: Berdugo
authors.forename: Pascal
authors.initials: P
authors.lastname: Bigey
authors.forename: Pascale
authors.initials: P
authors.lastname: Massin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Jeanny
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000378:metabolism / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005451:Fluorescein Angiography; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008566:Membranes / Q000378:metabolism / Q000473:pathology; D055806:Microvessels / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D051381:Rats; D012171:Retinal Vessels / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: C000608036:PGF protein, human; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D016650:Fluorescein-5-isothiocyanate