A small biomimetic collagen IV derived peptide reduces leakage and suppresses ocular neovascularization in mouse models

Abstract

Purpose : To evaluate the efficacy of intravitreous (IVT) injection of a collagen IV derived peptide, AXT120, in mouse models of choroidal neovascularization (CNV), retinal NV (RNV), subretinal leakage and retinal detachment (RD).

Methods : C57BL/6J mice had laser photocoagulation-induced rupture of Bruch’s membrane followed by IVT injections of 0.1 or 1μg of AXT120, 40μg of aflibercept, a combination of AXT120 and aflibercept, or control peptide. For regression of CNV, mice were treated 7 days post laser induction. CNV area was quantified 2 weeks after laser. At postnatal day (P) 12 mice with ischemic-induced retinopathy (OIR) were treated with AXT120 or control, and at P17 retinas were stained with GSA-Lectin to measure the area of RNV. At P20 rho/VEGF transgenic mice were treated with AXT120 or control and at P21 retinal flat mounts were double-stained with GSA-Lectin and anti-mouse serum albumin antibody for assessment of subretinal NV and leakage. Tet/Opsin/VEGF transgenic mice had IVT injection of AXT120 or control peptide. On day 6 after doxycycline was initiated, OCT scan was performed and it was noted whether there was no retinal detachment, partial RD or total RD.

Results : A significant decrease in the area of CNV was found in eyes treated with AXT120 (0.0026±0.0004), aflibercept (0.0014±0.0002), and the combination of AXT120 and aflibercept (0.0021±0.0008), compared to the control (0.009±0.003). Eyes treated with AXT120 (0.013±0.002) showed regression of CNV compared to control (0.031±0.005) and to the baseline group (0.023±0.004). Retinal flat mounts from OIR mice showed higher number of tufts of RNV in the control group (0.018±0.002) compared to AXT120-treated eyes (0.010±0.001). Rho/VEGF transgenic mice treated with AXT120 (0.005±0.002) showed significantly less leakage in the retina than the control-treated eyes (0.026±0.004). High power magnification of retinal flat mounts from rho/VEGF transgenic mice from AXT120-treated eyes showed significantly decrease in subretinal NV (0.008±0.002) compared to the control (0.018±0.001). Tet/Opsin/VEGF transgenic mice treated with AXT120 showed significant protective effect on preventing retinal detachment compared to the control group.

Conclusions : IVT injection of AXT120 suppresses choroidal and retinal NV, reduces retinal leakage, prevents retinal detachment in murine model and may provide a new treatment for neovascular AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.