title: Processing of chromogranins/secretogranin in patients with diabetic retinopathy.
abstract: OBJECTIVE
  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 α1-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.
authors.affiliation: Department of Ophthalmology, University Hospital of Strasbourg, Strasbourg, France; Physiopathology of Nervous System, University of Strasbourg, INSERM Z575, Strasbourg, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
authors.forename: David
authors.initials: D
authors.lastname: Gaucher
authors.forename: Jean-F
authors.initials: JF
authors.lastname: Chich
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bach
authors.forename: Peiman
authors.initials: P
authors.lastname: Shooshtarizadeh
authors.forename: Serge
authors.initials: S
authors.lastname: Picaud
authors.forename: Tristan
authors.initials: T
authors.lastname: Bourcier
authors.forename: Claude
authors.initials: C
authors.lastname: Speeg-Schatz
authors.forename: Jean M
authors.initials: JM
authors.lastname: Strub
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
authors.forename: Dominique
authors.initials: D
authors.lastname: Aunis
authors.forename: Marie-H
authors.initials: MH
authors.lastname: Metz-Boutigue
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D015153:Blotting, Western; D056148:Chromatography, Reverse-Phase; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism*; D053378:Chromogranin B / Q000235:genetics / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D053381:Secretogranin II / Q000235:genetics / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D057586:Vitreoretinal Surgery; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000096:biosynthesis
chemical_list: D053379:Chromogranin A; D053378:Chromogranin B; D010446:Peptide Fragments; D053381:Secretogranin II; D000515:alpha 1-Antitrypsin