PMID- 34532386 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220828 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 15 DP - 2021 Aug TI - LXA4 protects against blue-light induced retinal degeneration in human A2E-laden RPE cells and Balb-c mice. PG - 1249 LID - 10.21037/atm-21-3390 [doi] LID - 1249 AB - BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of permanent visual impairment in the elderly. Blue light (BL) has been reported to cause retinal damage and contribute to the onset and development of severe AMD. N-retinylidene-N-retinylethanolamine (A2E), a lipofuscin fluorophore, accumulates with ageing in the retinal pigment epithelium (RPE) cells. Once exposed to BL, A2E easily oxidizes to A2E-epoxides, causing oxidative-stress injury to the retina. Lipoxin A4 (LXA4), an endogenous anti-antioxidant lipid, plays a key role in multiple organs by binding to the formyl-peptide receptor-like 1 (FPRL1). This study examined the protective effects of LXA4 on oxidative-stress injury induced by BL exposure, and clarified the underlying mechanisms in cultured RPE cells and Balb-c mice. METHODS: LXA4 diluent was orally administered to mice before retinal degeneration was established. Optical coherence tomography, retinal histology, and RPE cell injury were assessed. RESULTS: LXA4 administration significantly ameliorated retinal damage as evidenced by the thicknesses of the retinal layers and the tight junctions of RPE cells in vivo. LXA4 inhibited BL-induced reactive oxygen species (ROS) production, reduced tight junctions, and the death of A2E-laden RPE cells. LXA4 also potently increased the expression of haem oxygenase-1 (HO1) and NAD(P)H quinone oxidoreductase 1 (NQO1), probably by decreasing the association between nuclear factor erythroid 2-related factor 2 (NRF2) and Kelch-like ECH (Epichlorohydrin) -associated protein 1 (Keap1), and ameliorating NRF2 nuclear translocation and the antioxidant response element (ARE) deoxyribonucleic acid (DNA) binding activity. CONCLUSIONS: Our results showed that LXA4 ameliorated retinal degeneration, and should be considered in the prevention and treatment of AMD. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Xie, Tianhua AU - Xie T AD - Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China. AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Cai, Jiping AU - Cai J AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Yao, Yong AU - Yao Y AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Sun, Chao AU - Sun C AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Yang, Qian AU - Yang Q AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Wu, Meili AU - Wu M AD - Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Xu, Zifan AU - Xu Z AD - Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. FAU - Sun, Xiaodong AU - Sun X AD - Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China. FAU - Wang, Xiaolu AU - Wang X AD - Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8421929 OTO - NOTNLM OT - Age-related macular degeneration (AMD) OT - blue light OT - lipoxin A4 (LXA4) OT - oxidative stress OT - retinal degeneration COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-3390). The authors have no conflicts of interest to declare. EDAT- 2021/09/18 06:00 MHDA- 2021/09/18 06:01 PMCR- 2021/08/01 CRDT- 2021/09/17 07:19 PHST- 2021/06/08 00:00 [received] PHST- 2021/08/05 00:00 [accepted] PHST- 2021/09/17 07:19 [entrez] PHST- 2021/09/18 06:00 [pubmed] PHST- 2021/09/18 06:01 [medline] PHST- 2021/08/01 00:00 [pmc-release] AID - atm-09-15-1249 [pii] AID - 10.21037/atm-21-3390 [doi] PST - ppublish SO - Ann Transl Med. 2021 Aug;9(15):1249. doi: 10.21037/atm-21-3390.