Fig. 6 ABTAA reduces hypoxia in RPE-choroid complex surrounding the CNV lesions. ABTAA reduces hypoxia in RPE-choroid complex surrounding the CNV lesions.

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Fig. 6 ABTAA reduces hypoxia in RPE-choroid complex surrounding the CNV lesions. ABTAA reduces hypoxia in RPE-choroid complex surrounding the CNV lesions. (A) Diagram of schedule for induction of CNV at D0; intravitreal administration of Fc, VEGF-Trap, or ABTAA (5 μg each) at D1; and their analyses at D4. (B) Images of pimonidazole staining to detect hypoxia in CNV and the surrounding RPE-choroid complex (area demarcated by the white dotted boundary) at the site of laser injury. Scale bars, 100 μm. (C) Comparisons of pimonidazole+ hypoxic areas. Error bars represent means ± SD. Each group, n = 10. *P < 0.05, **P < 0.005 versus Fc by one-way ANOVA followed by Student-Newman-Keuls post-test. (D) Schematic diagrams depicting how ABTAA functions as an alternative, combinative treatment of NV-AMD. In normal eyes, the outer retinal layers including the RPE are supplied by diffusion from the choriocapillaris. NV-AMD is featured by the development of CNV, leading to vascular leakage and macular edema. In NV-AMD, loss of choriocapillary causes hypoxia in RPE and adjacent cells, which induces the production of VEGF, a key player in leaky neovascularization. VEGF blockades, the current treatment of choice, effectively inhibit CNV and macular edema. However, because VEGF has a central role in the maintenance of choriocapillaris, VEGF blockades could aggravate the hypoxic environments by further promoting the loss of choriocapillaris and RPE damage. On the other hand, ABTAA-induced Tie2 activation not only inhibits CNV and suppresses vascular leakage but also promotes regeneration of choriocapillaris, subsequently alleviating hypoxia and leading to a favorable transition of the CNV microenvironment to prevent recurrence of NV-AMD. Jaeryung Kim et al. Sci Adv 2019;5:eaau6732 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).