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This abstract is assigned to session BGS: Belgian Glaucoma Society

Title

Differential effects of various VEGF isoforms on endothelial cells and Tenon fibroblasts

Purpose	To clarify the differential effects elicited by VEGF isoforms in scar formation after glaucoma surgery, we compared the biological responses and signaling pathways activated by the various isoforms on endothelial cells (HUVEC) and Tenon fibroblasts (TF) in vitro.
Methods	VEGF-R2 and neuropilin-1 (NRP-1) expression was analyzed on HUVEC and TF by RT-PCR. The effect of different VEGF isoforms (VEGF189, VEGF165 and VEGF121) on HUVEC and TF proliferation was determined by WST-1 assay. The extracellular signal-regulated kinase (ERK) pathway was evaluated by TransAM c-Myc assay.
Results	HUVEC showed a higher expression of VEGF-R2 and NRP-1 mRNA as compared to TF. VEGF189 only significantly increased the growth of TF, whereas VEGF165 only significantly increased HUVEC proliferation. VEGF165 strongly binds VEGF-R2 and NRP-1. As such, the combined reduced expression of VEGF-R2 and NRP-1 on TF explained why VEGF165 was more potent in inducing proliferation of HUVEC as compared to TF. VEGF121 exerted significant proliferative effects on both cell types by binding VEGF-R2. However, similar concentrations of VEGF121 stimulated HUVEC more than TF, due to the lower expression of VEGF-R2 on TF. All these stimulating effects on proliferation were associated with an activation of the ERK pathway.
Conclusion	Our data indicate that VEGF165 and VEGF121 predominantly affect blood vessel growth, whereas VEGF189 may be more important in fibrosis. Selective inhibition of VEGF165 (pegaptanib) may therefore be less effective to reduce ocular scar formation than non-selective VEGF-inhibition (bevacizumab), presumably due to retained action of VEGF121 and VEGF189.

Author 1

Last name	VAN BERGEN
Initials	T
Department	KUL (Oogziekten)
City	Leuven

Author 2

Last name	Vandewalle
Initials	E
Department	KUL (Oogziekten)
City	Leuven

Author 3

Last name	Van de Veire
Initials	S
Department	KUL (Oogziekten)
City	Leuven

Author 4

Last name	Moons
Initials	L
Department	KUL (Biologie)
City	Leuven

Author 5

Last name	Stalmans
Initials	I
Department	KUL (Oogziekten)
City	Leuven