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Chang Luo, Mei Chen, Rosana G. Penalva, Jiawu Zhao, Jiansu Chen, Shibo Tang, Heping Xu; Long-term Low-dose Aspirin Exacerbates Laser-induced Choroidal Neovascularization Through Down-regulating Thrombospondin-1 Expression. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5557.
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© ARVO (1962-2015); The Authors (2016-present)
Recent evidence suggests that long-term, low-dose aspirin intake increases the risk of neovascular age-related macular degeneration (nAMD) although the underlying mechanism remains poorly defined. This study investigated the role of long-term, low-dose aspirin intake in mouse model of laser-induced choroidal neovascularization (CNV).
Young (3-month old) and old C57BL/6J mice (16-month old) received daily oral administration of 0.04 mg/mouse aspirin for 8 weeks followed by CNV induction. Aspirin treatment continued for another week before mice were sacrificed for sample collection. Eyes were collected for immunohistochemistry. Flow cytometry was conducted in blood samples using antibodies against CD4, CD8, CD11b, Gr1, B220, LFA1, ICAM1 and MHCII. Bone marrow-derived macrophages (BMDMs, defined as M0) were polarized to M1 (LPS+IFN-γ) or M2 (IL-4) with or without aspirin (1~100uM). Gene expression levels of cytokine and angiogenic factors were evaluated by real-time PCR.
Aged mice developed more severe CNV compared with young mice. Aspirin treatment significantly increased the size of CNV in both young and aged mice, and the increment was more pronounced in young mice. The population of CD11b, Gr1 and MHCII+ cells was increased following CNV induction. Aspirin treatment did not significantly affect immune cell constitution. LPS+IFN-γ treatment significantly increased the expression of TNF-α, IL-1β, CCL2, IL-6, and thrombospondin-1 (TSP-I). Aspirin treatment significantly suppressed LPS+IFN-γ-induced upregulation of IL-1β. The treatment totally prevented LPS+IFN-γ-induced upregulation of TSP-1. VEGF expression in BMDMs was not affected by aspirin treatment.
TSP-1 is an anti-angiogenic growth factor that is known to play an important role in retinal homeostasis. Our results suggest that long-term, low-dose aspirin intake may increase the risk of nAMD by suppressing TSP-1 production.
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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