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Raquel Formica, Sean Hackett, Zibran Hafiz, Adam Mirando, Jordan J Green, Aleksander S Popel, Niranjan B Pandey, Peter A Campochiaro; AXT107, a Peptide that Disrupts Integrins, Suppresses Vascular Leakage in the Setting of Ocular Inflammation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4073.
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© ARVO (1962-2015); The Authors (2016-present)
AXT107, a collagen IV-derived peptide, which blocks signaling through VEGF receptors and activates Tie2, suppresses vascular leakage in ischemic retinopathy. In this study, we tested the effect of AXT107 on vascular leakage in a model of uveitis.
Adult C57BL/6 mice were given an intravitreous (IVT) injection of 125 ng of LPS in one eye and PBS in the other eye. At 4 and 24 hours after injection, retinal levels of mRNA for Angiopoietin 2 (Angpt2) and Interleukin-6 (IL-6) were measured by qRT-PCR. At 24 hours after IVT injection of 1 µg of AXT107 in one eye and PBS in the fellow eye, mice had IVT injection of 250 ng of LPS in both eyes. After 48 hours, the concentration of albumin in vitreous samples was measured by ELISA.
The relative gene expression levels of mRNA for Angpt2 in the retina was significantly higher 24 hours after injection of LPS (2.6±0.2) versus injection of PBS (1.01±0.09). As a positive control, the mRNA for the inflammatory cytokine IL-6 relative gene expression levels was markedly elevated (3000±1000 versus 0.7±0.2, respectively). There was a large increase in serum albumin concentration (mg/ml) in the vitreous 24 and 48 hours after injection of LPS indicating retinal vascular leakage. At 48 hours after injection of LPS, compared with eyes pretreated with PBS, those pretreated with AXT107 showed a significant reduction in vitreous albumin concentration (0.03±0.02 versus 0.05±0.02).
AXT107 suppresses inflammation-induced vascular leakage in a uveitis model and therefore may be useful for the treatment of macular edema in patients with ocular inflammatory disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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