Abstract
Purpose :
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 18 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 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-MFAP4 (2mg), ranibizumab (Lucentis 0.5mg) or remained as untreated controls. Lesions were then measured one and two months after the treatments using FA. Three of the control animals and one of the ranibizumab animals were lost to imaging due to cloudiness.
Results :
The vascular area of the CNV lesions were significantly reduced after 1 month (p<0.05), 2 months (p<0.001) and were sustained for 6 months after intravitreal injection with 2mg anti-MFAP4 (n = 12 of 6 rabbits). The 0.5mg Lucentis-treated (n = 10 of 5 rabbits) group had reduced lesion size only after 4 and 6 months compared with initial measurement. (2-way ANOVA with post hoc Tukey test). At each time point the anti-MFAP lesion size was smaller than anti-VEGF lesion size (p<0.001, two way ANOVA)
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 abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.