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Amir R. Hajrasouliha, Guomin Jiang, Huayi Lü, Wei Wang, Henry J. Kaplan, Hui Shao; Exosomes From Retinal Astroglial Cells (RACs) Suppressed New Vessel Formation In a Laser-induced CNV Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2016.
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Choriodal neovascularization (CNV) is a devastating complication of age-related macular degeneration (AMD), a leading cause of blindness in the developed world. In this study, we tested whether the exosomes released from normal tissue cells is an alternative and better therapy for CNV.
CNV in C57BL/B6 (B6) mice was induced by 4 laser spots (50um diameter at 250mV, 0.5s energy) around the optic disc. Exosomes released from cultured murine retinal astroglial cells (RAC), RPE, fibroblasts or dendritic cells (DC) were isolated. Mice with CNV were injected periocularly (in sub-Tenon’s space) with PBS or derived exosomes daily starting on day 0. On day 7 mice were perfused with PBS containing 50 mg/ml fluorescein-labeled dextran (FITC-dextran). The incidence of active CNV was observed in vivo by fluorescence microscopy. The incidence and area of new vessel formation in the choroid was determined in choroid flat mounts using fluorescent microscopy. Macrophage infiltration into CNV lesions was evaluated by immunostaining with F4/80 Ab.
Exosomes were detected in the retina 15 min after peri-ocular injection. Active CNV was completely inhibited after treatment with RAC exosomes compared to 42% incidence in PBS-treated mice. On choroid flat mounts incidence of CNV was observed in 75% of control laser spots versus 40% in RAC-exosome treated group. In addition, RAC exosome-treated mice had 83% less area of new vessels in the choroid than those in PBS-treated mice. Macrophage infiltration was also significantly reduced in RAC exosome-treated group compared to control (27 ± 4 vs. 60 ± 13 macrophage per laser spot, respectively, P<0.05). Exosomes derived from RACs had the strongest treatment efficacy compared to RPE, fibroblast and DC derived exosomes.
RAC exosomes contain anti-angiogenic molecules that can inhibit active CNV. Thus, RAC exosomes may represent a novel treatment for CNV in AMD.
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