Abstract
Purpose :
Purpose: Age-Related Macular Degeneration (AMD) is the leading cause of blindness in Europe, the USA and Australia. This study tested that targeting MFAP4 would reduce choroidal vessel growth, permeability and inflammation following laser induced choroidal neovascularisation in murine eyes.
Methods :
Methods: Female C57/Bl6 mice were anaesthetised and laser coagulation of the Bruch’s membrane was performed (Phoenix Micron IV retinal imaging microscope). Intraocular injection of either 1mg mouse IgG (R&D systems) 1 or 5mg humanized aMFAP4 or 1mg aVEGF. Injections were performed using a 36 Gauge Hamilton syringe, in a total of 2ml. Injections were performed at day 0 and day 7 or 14 post CNV for a fibrosis prevention trial. Fundus Fluorescein Angiography (FFA) was performed on day 7 and day 35. Mice were culled and eyes excised, fixed in 4% paraformaldehyde. Choroids were dissected and immunostained for isolectin IB4, CD45 and Collagen 1 and imaged by confocal microscopy. Quantification of lesion size, both of FFA and confocal data was performed using ImageJ.
Results :
Results: aMFAP4 (1mg or 5mg, n=8) reduced average lesion size and density (measured by FFA) at day 35 dose dependently (p<0.05 vs IgG control, n=5) with an approximately equal efficacy to anti-VEGF treatment in the prevention trial whether given at a single or double time point. IB4/CD45/Collagen 1 staining of flat-mounted choroids demonstrated limited anti angiogenic effect, but significant reduction in both fibrotic area and inflammatory cell infiltrate following 1mg when injected as a tri-weekly prevention regime. With greater efficacy than anti-VEGF injection (p<0.005, n=8).
Conclusions :
Conclusions: MFAP4 inhibition has previously shown efficiency in anti-angiogenic and anti-inflammatory trials, but here we show a modification of the regime to include longer and multiple treatments is also beneficial to reduce choroidal fibrosis. This may offer alternatives to traditional anti-angiogenic therapy in the management of wet AMD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.