title: Increased expression of angiogenic and inflammatory proteins in the vitreous of patients with ischemic central retinal vein occlusion.
abstract: BACKGROUND
  Central retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO.
  
  
  METHODS
  Vitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray.
  
  
  RESULTS
  Expression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE).
  
  
  CONCLUSIONS
  Proteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach.
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ehlken
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Grundel
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Michels
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany; Hannover Medical School, Eye Hospital, Hannover, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Junker
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stahl
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Schlunck
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Lutz L
authors.initials: LL
authors.lastname: Hansen
authors.affiliation: Augenklinik, Universitätsklinikum Göttingen, Göttingen, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Feltgen
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Martin
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany.
authors.forename: Hansjürgen T
authors.initials: HT
authors.lastname: Agostini
authors.affiliation: Klinik für Augenheilkunde, Universitätsklinikum Freiburg, Freiburg, Germany; Hannover Medical School, Eye Hospital, Hannover, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Pielen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D012170:Retinal Vein Occlusion / Q000276:immunology* / Q000378:metabolism*; D014822:Vitreous Body / Q000276:immunology / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D018971:Insulin-Like Growth Factor Binding Protein 2; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D053506:Matrix Metalloproteinase 10