Inhibition of micro‐fibrillar associated protein 4 as a potential therapy targeting choroidal neovascularisation in age related macular degeneration

Abstract

PurposeTo evaluate inhibition of Micro‐Fibrillar Associated Protein 4 (MFAP4) on choroidal neovascularization (CNV) in a mouse model of age‐related macular degeneration (AMD).MethodsAll experiments complied with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Female C57BL/6J mice were subjected to laser‐induced CNV, and intravitreally injected with either 1 µg ±MFAP4, 5 µg ±MFAP4, 1 µg mouse IgG or 1 µg ±VEGF‐A on day 0 and day 7. Fluorescein angiography (FA) was undertaken at day 7 and day 14, and choroids stained for inflammation (CD45) and vasculature (isolectin B4, IB4).ResultsFA showed that injection of αMFAP4 reduced average lesion size and density on day 7 compared to IgG (p < 0.01) and αVEGF‐A positive controls (p < 0.05) and both αMFAP4 and αVEGF‐A reduced average lesion size and density by day 14 compared to IgG (p < 0.001 and p < 0.05 respectively). IB4 staining indicated that both αMFAP4 and αVEGF‐A reduced lesion fluorescence intensity (p < 0.05). Both αMFAP4 and αVEGF‐A treatments also reduced infiltration of macrophages into the lesion site (p < 0.01 and p < 0.05).ConclusionsThese results show that inhibition of MFAP4 results in a significant decrease in neovascular lesions in an animal model of AMD. The reduction in macrophage infiltration suggests a potential mechanism of action for anti‐MFAP4 treatment. Together, this suggests that inhibition of MFAP4 could be a potential novel AMD therapeutic.