Advanced glycation end products induce choroidal endothelial cell proliferation, matrix metalloproteinase-2 and VEGF upregulation in vitro

Graefes Arch Clin Exp Ophthalmol. 2002 Dec;240(12):996-1002. doi: 10.1007/s00417-002-0568-6. Epub 2002 Nov 19.


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.

Conclusion: AGEs stimulate CEC proliferation, MMP-2 secretion and VEGF upregulation and may be important promoters of CNV formation in exudative AMD in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Division / drug effects
  • Cells, Cultured
  • Choroid / blood supply*
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Glycation End Products, Advanced / pharmacology*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Pigment Epithelium of Eye / drug effects
  • Pigment Epithelium of Eye / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Glycation End Products, Advanced
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Matrix Metalloproteinase 2