Titre
Placental growth factor contributes to micro-vascular abnormalization and blood-retinal barrier breakdown in diabetic retinopathy.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kowalczuk, L.
Auteure/Auteur
Touchard, E.
Auteure/Auteur
Omri, S.
Auteure/Auteur
Jonet, L.
Auteure/Auteur
Klein, C.
Auteure/Auteur
Valamanes, F.
Auteure/Auteur
Berdugo, M.
Auteure/Auteur
Bigey, P.
Auteure/Auteur
Massin, P.
Auteure/Auteur
Jeanny, J.C.
Auteure/Auteur
Behar-Cohen, F.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1932-6203
Statut éditorial
Publié
Date de publication
2011
Volume
6
Numéro
3
Première page
e17462
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Résumé
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).
MATERIALS AND 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.
CONCLUSION: 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.
MATERIALS AND 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.
CONCLUSION: 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.
Sujets
PID Serval
serval:BIB_488216DC9365
PMID
Open Access
Oui
Date de création
2013-08-23T06:08:40.270Z
Date de création dans IRIS
2025-05-20T18:53:30Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
21408222_BIB_488216DC9365.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
5.68 MB
Format
Adobe PDF
PID Serval
serval:BIB_488216DC9365.P001
URN
urn:nbn:ch:serval-BIB_488216DC93655
Somme de contrôle
(MD5):c0b2545afed6a7f55f3ce071f89009b9