ArticleProceedings of the National Academy of Sciences of the United States of America2004
Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 305 papers.
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Who cites it
305 citing papers in PubMed, 734 citations in OpenAlex.
- Maternal Docosahexaenoic Acid Status during Pregnancy and Its Impact on Infant Neurodevelopment.Nutrients · 2020Trial
- Long term effects of lutein, zeaxanthin and omega-3-LCPUFAs supplementation on optical density of macular pigment in AMD patients: the LUTEGA study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2013Trial
- Dietary ω-3 fatty acid and fish intake and incident age-related macular degeneration in women.Archives of ophthalmology (Chicago, Ill. : 1960) · 2011Trial
- Biosynthesis and analytics of specialized pro-resolving mediators: facts and faults.Journal of lipid research · 2026Review
- Multifunctional Catechol-Functionalized Cellulose Hydrogels for the Minimally Invasive Treatment of Acute Optic Nerve Injuries.Advanced healthcare materials · 2026Article
- Lipoxin A 4 (LXA 4 ) for diabetic retinopathy (DR).Indian journal of ophthalmology · 2026Article
- Omega-3 Fatty Acids and Alzheimer's Disease: Toward a New Understanding of Neuroprotective Mechanisms and Intervention Strategies.Marine drugs · 2026Review
- Cell apoptosis in ischemic stroke: Focus on lipid metabolism.Neural regeneration research · 2026Article
- Resolvin D1 requires TLR2-FPR2 crosstalk for inflammation resolution and protection during ocular bacterial infection.Communications biology · 2026Article
- Advances in RPGR gene therapy for X‑linked retinitis pigmentosa: From preclinical insights to clinical application (Review).International journal of molecular medicine · 2026Review
- Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis.The Journal of clinical investigation · 2026Article
- Neutrophil efferocytosis in chronic inflammatory gastrointestinal diseases: mechanistic insights and therapeutic potential.Frontiers in immunology · 2026Review
- From anti-inflammation to pro-resolution: a new paradigm for specialized pro-resolving mediators in regulating neuroinflammation and repair after cerebral ischemia-reperfusion.Frontiers in immunology · 2026Review
- From Strain to Repair: A Targeted Review of Lipid Mediators Driving the Inflammatory Cascade Following Exercise.Sports medicine (Auckland, N.Z.) · 2026Review
- Neuroprotectin D1 regulating the inflammation and nerve restoration inInternational journal of ophthalmology · 2026Article
- Specialized Pro-Resolving Lipid Mediators and Dietary Omega-3/6 Fatty Acids in Selected Inflammatory Skin Diseases: A Systematic Review.Antioxidants (Basel, Switzerland) · 2025Review
- Reprogramming inflammation: Mechanisms and therapeutic targeting of eicosanoids and pro-resolving mediators.European journal of pharmacology · 2025Review
- Association Between Omega-3 Polyunsaturated Fatty Acids and Myopia: Results From the Two-Sample and Multi-Tissue Genomic Mendelian Randomization Study and KNHANES.Food science & nutrition · 2025Article
- A hypoxia research-driven path led to identifying neuroprotection mediators: an interview with Dr. Nicolas G. Bazan.Cell death discovery · 2025Article
- The Role of Endogenous Specialized Proresolving Mediators in Mast Cells and Their Involvement in Inflammation and Resolution.International journal of molecular sciences · 2025Review
245 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Docosahexaenoic acid (DHA) is a lipid peroxidation target in oxidative injury to retinal pigment epithelium (RPE) and retina. Photoreceptor and synaptic membranes share the highest content of DHA of all cell membranes. This fatty acid is required for RPE functional integrity; however, it is not known whether specific mediators generated from DHA contribute to its biological significance. We used human ARPE-19 cells and demonstrated the synthesis of 10,17S-docosatriene [neuroprotectin D1 (NPD1)]. This synthesis was enhanced by the calcium ionophore A-23187, by IL-1beta, or by supplying DHA. Under these conditions, there is a time-dependent release of endogenous free DHA followed by NPD1 formation, suggesting that phospholipase A(2) releases the mediator's precursor. Added NPD1 potently counteracted H(2)O(2)/tumor necrosis factor alpha oxidative-stress-triggered apoptotic RPE DNA damage. NPD1 also up-regulated the antiapoptotic proteins Bcl-2 and Bcl-x(L) and decreased proapoptotic Bax and Bad expression. Moreover, NPD1 (50 nM) inhibited oxidative-stress-induced caspase-3 activation. NPD1 also inhibited IL-1beta-stimulated expression of cyclooxygenase 2 promoter transfected into ARPE-19 cells. Overall, NPD1 protected RPE cells from oxidative-stress-induced apoptosis, and we predict that it will similarly protect neurons. This lipid mediator therefore may indirectly contribute to photoreceptor cell survival as well. Because both RPE and photoreceptor cells die in retinal degenerations, our findings contribute to the understanding of retinal cell survival signaling and potentially to the development of new therapeutic strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.