Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration

Hera, Ruxandra; Keramidas, Michelle; Peoc’h, Michel; Mouillon, Michel; Romanet, Jean-Paul; Feige, Jean-Jacques

doi:10.1016/j.ajo.2004.11.064

Next »American Journal of Ophthalmology
Volume 139, Issue 4 , Pages 589-596, April 2005

Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration

Ruxandra Hera, MD
- Department of Opthalmology, University Hospital of Grenoble, La Tronche, France
- INSERM EMI 01–05, Department of Cell Responses and Dynamics, Commissariat á l’Energie Atomique, Grenoble, France
- Ruxandra Hera and Michelle Keramidas contributed equally to this work.
Michelle Keramidas, MSc
- INSERM EMI 01–05, Department of Cell Responses and Dynamics, Commissariat á l’Energie Atomique, Grenoble, France
- Ruxandra Hera and Michelle Keramidas contributed equally to this work.
Michel Peoc’h, MD
- Department of Pathology, University Hospital of Grenoble, La Tronche, France
Michel Mouillon, MD
- Department of Opthalmology, University Hospital of Grenoble, La Tronche, France
Jean-Paul Romanet, MD
- Department of Opthalmology, University Hospital of Grenoble, La Tronche, France
Jean-Jacques Feige, PhD
- INSERM EMI 01–05, Department of Cell Responses and Dynamics, Commissariat á l’Energie Atomique, Grenoble, France
- Inquiries to Dr J. J. Feige, INSERM EMI 01-05, DRDC/ANGIO, CEA-G, 17 Rue des Martyrs, 38054 Grenoble Cedex 9, France; fax: (33) 438-785-058

Accepted 29 November 2004. published online 01 March 2005.

Purpose

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).

Design

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-μ 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).

Conclusion

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.

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This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM EMI 01–05) and by the University Joseph Fourier (UFR Médecine).

PII: S0002-9394(04)01463-1

doi:10.1016/j.ajo.2004.11.064

Next »American Journal of Ophthalmology
Volume 139, Issue 4 , Pages 589-596, April 2005

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