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I. F. Fournier, Jr., M.-H. Metz-Boutigue, Sr., M. Saleh, T. Bourcier, C. Speeg-Schatz, D. Gaucher; Vitreous Expression and Processing of Chromogranins in Patients With Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3306.
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Diabetic retinopathy (DR) is a chronic retinal disease, in which inflammation seems to plays an important role. Chromogranins (Cgs) are ubiquitous prohormormones implicated in several inflammatory diseases. An eventual relation between Cgs and DR has not been elucidated yet. The aim of this study was to analyse the expression and processing of Cgs in diabetic vitreous compared with non diabetic vitreous. Vitreous properties related to Cgs processing and inflammatory events were also studied to identify new mechanisms in DR physiopathology.
Vitreous samples from patients with DR (n=27)and non diabetic patients (n=28) were collected. Identification and expression quantification of Cgs in the vitreous humor were realised, using Western-blot, High Performance Liquid Chromatography (HPLC), Edman sequencing and mass spectrometry techniques. The effect of diabetic vitreous on polymorphonucear neutrophils (PMN) migration was also examined using a chemotaxis assay.
Cgs expression was higher in diabetic vitreous than in controls. In diabetic vitreous, long fragments of Cgs were overexpressed. Only small fragments of CgB were present in control vitreous. Interestingly, α1-antitrypsin (A1AT) was overexpressed in diabetic vitreous and migration of PMNs was increased in presence of diabetic vitreous.
Our results suggest an altered maturation of Cgs in DR. High level of A1AT may impair the proteolytic processing of Cgs and prevent the formation of active small Cgs derived peptides. As some of these peptides are known to have anti-Vascular Endothelial Growth Factor (VEGF) effects, their absence may lead to proangiogenic activity and participate to DR progression.
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