Placental growth factor contributes to micro-vascular abnormalization and blood-retinal barrier breakdown in diabetic retinopathy.

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License: CC BY 4.0
Serval ID
serval:BIB_488216DC9365
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Placental growth factor contributes to micro-vascular abnormalization and blood-retinal barrier breakdown in diabetic retinopathy.
Journal
Plos One
Author(s)
Kowalczuk L., Touchard E., Omri S., Jonet L., Klein C., Valamanes F., Berdugo M., Bigey P., Massin P., Jeanny J.C., Behar-Cohen F.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
6
Number
3
Pages
e17462
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
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).
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.
Keywords
Animals, Blood-Retinal Barrier/metabolism, Blood-Retinal Barrier/pathology, Diabetic Retinopathy/metabolism, Diabetic Retinopathy/pathology, Female, Fluorescein Angiography, Fluorescein-5-isothiocyanate/metabolism, Humans, Immunohistochemistry, Male, Membranes/metabolism, Membranes/pathology, Microvessels/abnormalities, Microvessels/metabolism, Middle Aged, Pregnancy Proteins/metabolism, Rats, Retinal Vessels/abnormalities, Retinal Vessels/metabolism, Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
23/08/2013 7:08
Last modification date
20/08/2019 13:55
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