Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration.
OBJECTIVE
Vascular endothelial growth factor (VEGF) and angiopoietins are key regulators of angiogenesis. The purpose of this study was to measure mRNA levels of these factors and of their receptors in surgically excised subfoveal membranes from patients with age-related macular degeneration (AMD) and to evaluate their relevance as prognostic markers of postsurgical recurrence of choroidal neovascularization (CNV).


METHODS
Prospective observational case series.


METHODS
setting: Institutional. study population: In a prospective series of 24 patients (aged 51 to 91 years) with classic CNV of AMD diagnosed less than 6 months previously, 24 subfoveal membranes (one eye per patient) were surgically removed and collected. Thirteen patients underwent treatment for recurrence of CNV within 6 months of surgery. main outcome measures: Four 8-mu sections were prepared from each membrane for immunohistochemical determination of vascular density (CD31 immunostaining). The remaining tissue was used for preparation of total RNA. The levels of VEGF-A, VEGF-R1, VEGF-R2, neuropilin-1, angiopoietin-1, angiopoietin-2, Tie-2, and hypoxanthine phosphoribosyltransferase mRNAs were determined by real-time reverse-transcriptase polymerase chain reaction.


RESULTS
Vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 appeared to be expressed to variable levels in most samples, whereas Tie-2, VEGF-R1, and VEGF-R2 were undetectable. Low levels of VEGF expression correlated with postsurgical recurrence of CNV (P = .07). Angiopoietin-1 and angiopoietin-2 levels did not predict recurrence (P > .1).


CONCLUSIONS
The results indicate that at the time of surgical excision, subfoveal membranes express angiopoietin-1, VEGF, and, to a lesser degree, angiopoietin-2. Because CNV appears to recur less often in membranes expressing high levels of VEGF, we hypothesize that VEGF acts as a stabilizer of neovessels at this stage of the disease.
Hera
Ruxandra
R
Department of Opthalmology, University Hospital of Grenoble, La Tronche, France.
Keramidas
Michelle
M
Peoc'h
Michel
M
Mouillon
Michel
M
Romanet
Jean-Paul
JP
Feige
Jean-Jacques
JJ
D000368:Aged; D000369:Aged, 80 and over; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000601:surgery; D005584:Fovea Centralis / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008268:Macular Degeneration / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D039942:Neuropilin-1 / Q000235:genetics; D011183:Postoperative Complications; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D014821:Vitrectomy
D042682:Angiopoietins; D015415:Biomarkers; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D007041:Hypoxanthine Phosphoribosyltransferase; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2