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Angiogenic Factors Expressed in Cells Cultured from Normal RPE and RPE from Choroidal Neo-vascular Membranes

Martin G., Agostini H., Hansen L. L.,
Albert-Ludwigs-Universität, Augenklinik (Freiburg)

Purpose: Choroidal neovascular (CNV) membranes cause loss of vision in age-related macular degeneration. Starting from the choroid, new capillaries penetrate Bruch's membrane and the retinal pigment epithelium (RPE). They are supposed to be attracted by angiogenic factors produced in the RPE. Thus, our aim is to investigate the expression and regulation of angiogenic factors in the RPE.
Methods: Quantitative PCR on cDNA from RPE cell cultures. Normal RPE cultures (ARPE-19) were compared to RPE cultures from choroidal neovascular membranes (CNV-RPE).
Results: Most of the angiogenic factors tested were expressed both in ARPE-19 and in CNV-RPE cells. Some were equally detected in both cell types, but most of them were more abundant in CNV-RPE. The angiogenic factors VEGF-A, VEGF-B, and VEGF-C as well as the receptor VEGF-R2 were detected both in ARPE-19 and in CNV-RPE. VEGF-R1 and VEGF-R3 were expressed very weakly. Semaphorin-3A and the receptors neuropilin-1 (NRP1) and NRP2 were found in both cell types. Angiopoietin-1 and angiopoietin-2 were weakly expressed, and their receptor Tie-2 was not detectable. The growth factors FGF-2 and PEDF were detected as well as the hypoxia-inducible factor (HIF1). Significant increase in CNV-RPE compared to ARPE-19 was observed for VEGF-R1, NRP2, FGF-2, and PEDF as well as for angiopoietin-1 and angiopoietin-2.
Conclusions: A set of common angiogenic factors was detected both in ARPE-19 cells and in CNV-RPE cells. Thus, the RPE has the potential to promote angiogenesis in age-related macular degeneration. Though a lot is known about VEGFA, VEGFR2, and NRP1, the mechanisms and consequences of the enhanced expression of VEGF-R1 and NRP2 as well as of FGF-2 and PEDF need further investigation.

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