Processing of chromogranins/secretogranin in patients with diabetic retinopathy

Aims: Inflammation has been linked to the development of diabetic retinopathy (DR). Chromogranins A, B (CgA, CgB) and secretogranin II (SgII), are prohormones overexpressed in inflammatory diseases. The present study was conducted to evaluate the presence and processing of these prohormones in the vitreous of patients with DR (DV), compared with nondiabetic vitreous (NDV). Methods: Thirteen DV and 14 NDV samples were collected during vitreoretinal surgery. ELISA. Western blot, RP-HPLC, dot blot, protein sequencing and mass spectrometry were used to study the quantitative expression and the processing of CgA, CgB and SgII. Results: CgA, CgB and SgII presence was higher in DV than in NDV. Mean concentration of CgA evaluated by ELISA was 90.8 (+/- 90.1) n L(-1) in DV vs. 29.7 (+/- 20.9) in NDV (p = 0.039). In NDV, Western blot indicated that only short CgB-derived peptides were identified. In DV, proteomic analyses showed that long CgA-, CgB- and SgII-derived fragments and alpha 1-antitrypsin were overexpressed, suggesting possible inhibition of the proteolytic process. Conclusions: This study shows differences in the presence and endogenous processing of CgA, CgB and SgII from DV vs. NDV. In DV, the increase of complete granins and the attenuation of their endogenous proteolytic processing could participate in DR progression by reducing the presence of regulatory peptides, important for the pro-/anti-angiogenic balance in the eye. (C) 2010 Published by Elsevier B.V.