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This abstract is assigned to session OB Free papers 3 - Medical retina

Title

Efficacy of Placental growth factor Inhibition in AMD

Purpose	We previously showed that an anti-PlGF antibody (5D11D4) inhibits choroidal neovascularization (CNV) in a mouse model of AMD. An additive effect was shown in combination therapy with an anti-VEGFR antibody. Specificity of 5D11D4 was assessed in this study.
Methods	CNV was induced in mice by placing 3 laser burns on the choroid. Mice with a genetic loss of PlGF; a lacking tyrosin kinase domain of the Flt-1R or a knock-down of the monocyte chemoattractive protein were generated. The optimal dose of 25mg/kg of 5D11D4 was injected in all mice ip. 3 times a week.
Results	In a first experiment loss of PlGF inhibited CNV. However, administration of 5D11D4 to PlGF-/- mice did not inhibit CNV further than in control-treated PlGF-/- mice. Second, CNV lesions in Ccl2-/- mice were slightly larger than in WT mice within 14 days after laser-injury. Notably, 5D11D4 was able to inhibit CNV again by 53%. Third, CNV lesions were reduced by 70% in Flt1-TK-/- mice, comparably as observed in PlGF-/- mice. 5D11D4 was unable to inhibit CNV in Flt1-TK-/- mice any further, suggesting that PlGF works specifically via Flt1. Fourth, we also tested the murine anti-human PlGF mAb 16D3 in humanized PlGF-/- mice. Human PlGF-2 increased laser-induced CNV after 5 days, but this increase was again blocked by 16D3. And finally, of two other anti-mPlGF mAbs, 3C7A8 and 12H6B6, the first one inhibited CNV, while 12H6B6 was ineffective, showing that anti-PlGF mAb clones with proven efficacy in vitro are not necessarily effective in blocking PlGF-driven processes in vivo.
Conclusion	We have proven that 5D11D4 specifically inhibits laser-induced CNV formation, in different transgenic models and that this effect is mediated via the Flt1 receptor.

Author 1

Last name	VAN DE VEIRE
Initials	S
Department	UZL
City	Leuven

Author 2

Last name	Van Bergen
Initials	T
Department	KUL
City	Leuven

Author 3

Last name	Moons
Initials	L
Department	KUL
City	Leuven

Author 4

Last name	Carmeliet
Initials	P
Department	KUL
City	Leuven

Author 5

Last name	Stalmans
Initials	I
Department	UZL
City	Leuven