title: Advanced glycation end products induce choroidal endothelial cell proliferation, matrix metalloproteinase-2 and VEGF upregulation in vitro.
abstract: BACKGROUND
  Advanced glycation end products (AGEs) are considered to be important modulators of angiogenesis and accumulate in choroidal neovascularization (CNV). Their effects regarding cells involved in proliferation of CNV [retinal pigment epithelial (RPE) cells, Müller cells and choroidal endothelial cells (CECs)] were investigated. Furthermore, the effects of AGEs on expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) by CECs were explored.
  
  
  METHODS
  RPE cells, CECs and Müller cells were exposed to AGEs (10 microg/ml, 50 microg/ml and 100 microg/ml) for a time course of three days in their desired medium and proliferation was estimated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. MMP-2 expression of AGE-stimulated CECs was determined by zymography and reverse-transcription polymerase chain reaction (RT-PCR) after 36 h of exposure. Furthermore, VEGF expression of AGE-stimulated CECs (50 microg/ml and 100 microg/ml) was determined by RT-PCR after an exposure time of 36 h.
  
  
  RESULTS
  AGEs in a concentration of 50 microg/ml and 100 microg/ml increased the proliferation of CECs (41% vs 46.1%; P<0.005). No AGE effect on RPE cell and Müller cell proliferation was seen. AGEs in all concentrations used upregulated the VEGF mRNA expression of CECs. Zymography and RT-PCR demonstrated the upregulation of MMP-2 by CECs after AGE exposure.
  
  
  CONCLUSIONS
  AGEs stimulate CEC proliferation, MMP-2 secretion and VEGF upregulation and may be important promoters of CNV formation in exudative AMD in vivo.
authors.affiliation: Department of Ophthalmology, University of Leipzig, Liebigstrasse 10-14, 03411 Leipzig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hoffmann
authors.forename: U
authors.initials: U
authors.lastname: Friedrichs
authors.forename: W
authors.initials: W
authors.lastname: Eichler
authors.forename: A
authors.initials: A
authors.lastname: Rosenthal
authors.forename: P
authors.initials: P
authors.lastname: Wiedemann
mesh_terms: D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D017127:Glycation End Products, Advanced; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020778:Matrix Metalloproteinase 2