Title | FRO: Anti-PLGF, a safer alternative to anti-VEGF, in the treatment of AMD? |
Purpose | To 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. |
Methods | At 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. |
Results | Combination 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. |
Conclusion | Overall, 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. |
Last name | VAN DE VEIRE |
Initials | S |
City | Leuven |
Last name | VINORES |
Initials | S |
Last name | MAZZONE |
Initials | M |
Last name | VAN BERGEN |
Initials | T |
Last name | STASSEN |
Initials | JM |
Last name | MOONS |
Initials | L |
Last name | STALMANS |
Initials | I |
Last name | CARMELIET |
Initials | P |