title: Differential expression of vascular endothelial growth factor-a isoforms in neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To investigate the role of vascular endothelial growth factor-A (VEGF-A) isoforms in neovascular age-related macular degeneration.
  
  
  METHODS
  Choroidal neovascular membranes (CNV) were excised in 24 patients, 8 of them underwent previous photodynamic therapy. All procedures were performed before anti-VEGF therapies were implemented in Germany. Normal human donor eyes served as controls. Messenger RNA expression of total VEGF-A and VEGF-A isoforms was measured.
  
  
  RESULTS
  Vascular endothelial growth factor-A121 is the most abundant isoform in CNV and control tissues. In controls, VEGF-A121 is lowest in neural retina and highest in choroids. For total VEGF-A and VEGF-A165, this is vice versa. VEGF-A165 and VEGF-A189 are significantly higher in CNV than in control choroids, the opposite is found for VEGF-A121. After photodynamic therapy, total VEGF-A and VEGF-A121 are increased, VEGF-A165 and VEGF-A189 are decreased. Age-dependently, there is an increase in VEGF-A165 and a decrease in VEGF-A121.
  
  
  CONCLUSIONS
  Vascular endothelial growth factor-A isoforms are differentially distributed, suggesting that tissue-specific regulation of various isoforms is physiologically important. The disruption of this homeostasis in CNV membranes may be significant in the onset and progression of neovascular age-related macular degeneration. Our findings support the dominant role of VEGF-A121 in neovascular age-related macular degeneration but hint that VEGF-A165 may have an equivalent role in other neovascular retinal pathology.
authors.affiliation: *Department of Ophthalmology, University of Luebeck, Luebeck, Germany; and †Department of Ophthalmology, Hacettepe University, Ankara, Turkey.
authors.forename: Swaantje
authors.initials: S
authors.lastname: Grisanti
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.forename: Olcay
authors.initials: O
authors.lastname: Tatar
authors.forename: Julia
authors.initials: J
authors.lastname: Lueke
authors.forename: Matthias
authors.initials: M
authors.lastname: Lueke
authors.forename: Aysegul
authors.initials: A
authors.lastname: Tura
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
mesh_terms: D000368:Aged; D020256:Choroidal Neovascularization / Q000235:genetics / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D010778:Photochemotherapy; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014821:Vitrectomy; D057135:Wet Macular Degeneration / Q000235:genetics* / Q000601:surgery
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A