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TitleFRO: Anti-PLGF, a safer alternative to anti-VEGF, in the treatment of AMD?
PurposeTo design additional or adjunctive therapeutic strategies to improve the efficacy and safety of the current treatment options for CNV. The efficacy and safety of anti-PlGF therapy in combination with the golden standards of AMD treatment was checked.
MethodsAt first, to assess the ability of anti-PlGF to suppress CNV, a laser-induced murine CNV model was used and the size and vascular component of the lesions were evaluated on choroidal flat-mounts and serial sections.
ResultsCombination treatment of anti-PlGF with an antibody to VEGFR2 increased the CNV suppression to 70%, providing evidence that both VEGF and PlGF are implicated and that targeting both molecules may be more effective than monotherapy. Anti-PlGF also suppressed the local inflammation associated with CNV lesions with ± 35%, while anti-VEGFR2 did not. Moreover, PlGF reduced the amount of vascular leakage into the retina after CNV, and blood-retinal barrier breakdown associated with diabetic retinopathy. These are both mechanistic features of macular edema. Anti-PlGF treatment prove to be safe. Anti-PlGF did not influence the normal retinal vascular development. Nor did it cause retinal neurodegeneration in eyes with and without photoreceptor degeneration. Contrary to anti-PlGF, anti-VEGFR2 at therapeutic levels impaired normal vascular development in retina, kidney, and heart.
ConclusionOverall, our study already allowed us to unravel partially the role of PlGF in CNV and the therapeutic potency and safety of anti-PlGF antibodies in the treatment of this disease. With these efforts we are hoping to improve the visual prognosis of the vast population suffering from this blinding disease.
Author 1
Last nameVAN DE VEIRE
InitialsS
CityLeuven
Author 2
Last nameVINORES
InitialsS
Author 3
Last nameMAZZONE
InitialsM
Author 4
Last nameVAN BERGEN
InitialsT
Author 5
Last nameSTASSEN
InitialsJM
Author 6
Last nameMOONS
InitialsL
Author 7
Last nameSTALMANS
InitialsI
Author 8
Last nameCARMELIET
InitialsP
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