Abstract
Purpose :
New treatment strategies are needed to improve the disease management for patients who respond poorly to anti-VEGF treatments. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein and a ligand for avb3 and avb5 integrins. We previously showed that anti-MFAP4 antibodies (anti-MFAP4) effectively block pathological angiogenesis and inflammation in a mouse model of laser-induced choroidal neovascularization and in a rat model of diabetic retinopathy. Here, we report the efficacy of anti-MFAP4 in a rabbit model of CNV.
Methods :
CNV lesions were induced in 12 brown HyD rabbits by subretinal injection of 50µl of Matrigel containing 100ng FGF2 and 100ng LPS. Bruch’s membrane was perforated with a 30G micro-lancet to ensure a small subretinal hemorrhage from the choroidal vessels. The growth of lesions was observed using Optic Coherence Tomography (OCT), OCT-angiogram (OCTA), and Fluorescein Angiogram (FA) modules of a Heidelberg Spectralis. Once CNV growth had reached measurable size after one month, animals received 50µl intravitreal injections of anti-MFP4 (2mg), ranibizumab (Lucentis 0.5mg) or remained as untreated controls. Lesions were then measured one and two months after the treatments using OCT, OCTA and FA.
Results :
The lesions consistently mimic the classic CNV membranes in wet AMD with peripapillary neovascular growth and subretinal CNV connected to choroidal vessels, observed by FA and OCTA. The size of CNV lesions were significantly reduced after 1 month (p<0.05) and 2 months (p<0.001) intravitreal injection with 2mg anti-MFAP4 (6 lesions of 4 rabbits) and 0.5mg Lucentis-treated (8 lesions of 4 rabbits) group compared with control groups, corrected for initial size before treatment (2-way ANOVA with post hoc Tukey test). At 2 months the anti-MFAP lesion size was smaller than anti-VEGF lesion size (p=0.064, t test)
Conclusions :
We demonstrated a single intravitreal injection of anti-MFAP4 effectively reduced the CNV lesion size in the rabbit model. Using MFAP4 as alternative target to VEGF could be used as novel strategy, particularly in patients who respond poorly to anti-VEGF treatments.
This is a 2020 ARVO Annual Meeting abstract.