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

Autor: Elodie Touchard, Marianne Berdugo, Pascale Massin, Jean-Claude Jeanny, Laura Kowalczuk, Pascal Bigey, Laurent Jonet, Samy Omri, Christophe Klein, Francine Behar-Cohen, Fatemeh Valamanes
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
Placental growth factor
Time Factors
genetic structures
lcsh:Medicine
Pregnancy Proteins
Cardiovascular
Biochemistry
chemistry.chemical_compound
Blood-Retinal Barrier
Fluorescein Angiography
lcsh:Science
Peripheral Vascular Diseases
Multidisciplinary
medicine.diagnostic_test
Animal Models
Diabetic retinopathy
Middle Aged
Fluorescein angiography
Immunohistochemistry
medicine.anatomical_structure
Medicine
Retinal Disorders
Female
Fluorescein-5-isothiocyanate
Research Article
Biotechnology
medicine.medical_specialty
Biomedical Engineering
Blood–retinal barrier
Bioengineering
Model Organisms
Vascular Biology
Growth Factors
Ophthalmology
Diabetes mellitus
Internal medicine
medicine
Animals
Humans
Biology
Placenta Growth Factor
Retina
Diabetic Retinopathy
Membranes
business.industry
lcsh:R
Proteins
Retinal Vessels
Retinal
medicine.disease
eye diseases
Rats
Ciliary muscle
Endocrinology
chemistry
Microvessels
Rat
lcsh:Q
sense organs
Blood-Retinal Barrier/metabolism
Blood-Retinal Barrier/pathology
Diabetic Retinopathy/metabolism
Diabetic Retinopathy/pathology
Fluorescein-5-isothiocyanate/metabolism
Membranes/metabolism
Membranes/pathology
Microvessels/abnormalities
Microvessels/metabolism
Pregnancy Proteins/metabolism
Retinal Vessels/abnormalities
Retinal Vessels/metabolism
business
Zdroj: Plos One, vol. 6, no. 3, pp. e17462
PLoS ONE, Vol 6, Iss 3, p e17462 (2011)
PLoS ONE
Popis: 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.
Databáze: OpenAIRE
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