Oxidative medicine and cellular longevity, 2021, Vol.2021 (1), p.5520644
2021
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- Autor(en) / Beteiligte
- Titel
- P2X7 Receptor Antagonist Attenuates Retinal Inflammation and Neovascularization Induced by Oxidized Low-Density Lipoprotein
- Ist Teil von
- Oxidative medicine and cellular longevity, 2021, Vol.2021 (1), p.5520644
- Ort / Verlag
- United States: Hindawi
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Age-related macular degeneration (AMD) is a common and severe blinding disease among people worldwide. Retinal inflammation and neovascularization are two fundamental pathological processes in AMD. Recent studies showed that P2X7 receptor was closely involved in the inflammatory response. Here, we aim to investigate whether A740003, a P2X7 receptor antagonist, could prevent retinal inflammation and neovascularization induced by oxidized low-density lipoprotein (ox-LDL) and explore the underlying mechanisms. ARPE-19 cells and C57BL/6 mice were treated with ox-LDL and A740003 successively for in vitro and in vivo studies. In this research, we found that A740003 suppressed reactive oxygen species (ROS) generation and inhibited the activation of Nod-like receptor pyrin-domain protein 3 (NLRP3) inflammasome and nuclear factor-κB (NF-κB) pathway. A740003 also inhibited the generation of angiogenic factors in ARPE-19 cells and angiogenesis in mice. The inflammatory cytokines and phosphorylation of inhibitor of nuclear factor-κB alpha (IKBα) were repressed by A740003. Besides, ERG assessment showed that retinal functions were remarkably preserved in A740003-treated mice. In summary, our results revealed that the P2X7 receptor antagonist reduced retinal inflammation and neovascularization and protected retinal function. The protective effects were associated with regulation of NLRP3 inflammasome and the NF-κB pathway, as well as inhibition of angiogenic factors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1942-0900eISSN: 1942-0994DOI: 10.1155/2021/5520644Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8397555
- Format
- –
- Schlagworte
- Angiogenesis, Animals, Apoptosis, Cytokines - metabolism, Diabetes, Diabetic retinopathy, Inflammation, Inflammation - chemically induced, Inflammation - drug therapy, Inflammation - metabolism, Inflammation - pathology, Lipoproteins, LDL - toxicity, Macular degeneration, Male, Mice, Mice, Inbred C57BL, Neovascularization, Pathologic - chemically induced, Neovascularization, Pathologic - drug therapy, Neovascularization, Pathologic - metabolism, Neovascularization, Pathologic - pathology, NF-kappa B - genetics, NF-kappa B - metabolism, NLR Family, Pyrin Domain-Containing 3 Protein - genetics, NLR Family, Pyrin Domain-Containing 3 Protein - metabolism, Oxidative Stress, Pathogenesis, Photoreceptors, Purinergic P2X Receptor Antagonists - pharmacology, Reactive Oxygen Species - metabolism, Receptors, Purinergic P2X7 - chemistry, Receptors, Purinergic P2X7 - metabolism, Retinitis - chemically induced, Retinitis - drug therapy, Retinitis - metabolism, Retinitis - pathology, Signal Transduction