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Raquel Formica, Valeria E Lorenc, Niranjan B Pandey, Ji-kui Shen, Jayoung Kim, Aleksander S Popel, Jordan Green, Peter A Campochiaro; A small biomimetic collagen IV derived peptide reduces leakage and suppresses ocular neovascularization in mouse models. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3269. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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).
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.
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.
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.
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