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Rescue and repair during photoreceptor cell renewal mediated by docosahexaenoic acid-derived neuroprotectin D1
Open accessAbstract
Retinal degenerative diseases result in retinal pigment epithelial (RPE) and photoreceptor cell loss. These cells are continuously exposed to the environment (light) and to potentially pro-oxidative conditions, as the retina's oxygen consumption is very high. There is also a high flux of docosahexaenoic acid (DHA), a PUFA that moves through the blood stream toward photoreceptors and between them and RPE cells. Photoreceptor outer segment shedding and phagocytosis intermittently renews photoreceptor membranes. DHA is converted through 15-lipoxygenase-1 into neuroprotectin D1 (NPD1), a potent mediator that evokes counteracting cell-protective, anti-inflammatory, pro-survival repair signaling, including the induction of anti-apoptotic proteins and inhibition of pro-apoptotic proteins. Thus, NPD1 triggers activation of signaling pathway/s that modulate/s pro-apoptotic signals, promoting cell survival. This review provides an overview of DHA in photoreceptors and describes the ability of RPE cells to synthesize NPD1 from DHA. It also describes the role of neurotrophins as agonists of NPD1 synthesis and how photoreceptor phagocytosis induces refractoriness to oxidative stress in RPE cells, with concomitant NPD1 synthesis.
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“DHA is enriched in the CNS, which includes the retina (Bazan, 2009, 2007, 2006; Gordon and Bazan, 1990), and serves as the precursor for neuroprotective and prohomeostatic 22-carbon docosanoids (Bazan, 2009, 2007; Bazan et al., 2010; Mukherjee et al., 2004) and of 32- or 34-carbon ELVs (Bhattacharjee et al., 2017; Jun et al., 2017).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Bazan et al., 2010
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“Recent evidence suggests that omega-3 essential fatty acid improves neurological outcomes in models of epilepsy [14, 15] and is neuroprotective [12, 16, 17].”
From Hippocampal neuro-networks and dendritic spine perturbations in epileptogenesis are attenuated by neuroprotectin D1 (2015) · cites this paper as [16]
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Synthesis of arachidonoyl coenzyme A and docosahexaenoyl coenzyme A in retina
Reddy, T. S., & Bazan, N. G. (1984) · Current Eye Research · doi:10.3109/02713688409000826 · Cited by 34
Lee, S., Kim, J. H., Kim, J. H., Chung, M. J., Wen, Q., Chung, H., Kim, K. W., & Yu, Y. S. (2007) · PubMed · Cited by 33
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Neuroprotectin D1 inhibits retinal ganglion cell death following axotomy
Qin, Q., Patil, K., Gronert, K., & Sharma, S. C. (2008) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2008.09.022 · Cited by 31
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Synthesis of docosahexaenoyl-, arachidonoyl- and palmitoyl-coenzyme a in ocular tissues
Reddy, T. S., & Bazan, N. G. (1985) · Experimental Eye Research · doi:10.1016/0014-4835(85)90097-1 · Cited by 28
Reddy, T. S., & Bazan, N. G. (1985) · Journal of Neuroscience Research · doi:10.1002/jnr.490130305 · Cited by 27
NMDA Receptor-Stimulated Release of Arachidonic Acid: Mechanisms for the Bazan Effect
Horrocks, L. A., & Farooqui, A. A. (1994) · Springer eBooks · doi:10.1007/978-1-4615-1879-2_11 · Cited by 25
Butovich, I. A. (2005) · Journal of Lipid Research · doi:10.1194/jlr.c500015-jlr200 · Cited by 23
Activation of polyunsaturated fatty acids by rat tissues in vitro
Reddy, T. S., & Bazan, N. G. (1984) · Lipids · doi:10.1007/bf02534740 · Cited by 14
Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease
Municio, A. M., & Miras-Portugal, M. T. (1994) · Springer eBooks · doi:10.1007/978-1-4615-1879-2 · Cited by 7
A proposed role for all-trans retinal in regulation of rhodopsin regeneration in human rods
Navid, A., Nicholas, S. C., & Hamer, R. D. (2006) · Vision Research · doi:10.1016/j.visres.2006.07.035 · Cited by 5
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Pro-resolving lipid mediators are leads for resolution physiology
Serhan, C. N. (2014) · Nature · doi:10.1038/nature13479 · Cited by 3,041
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Serhan, C. N., & Levy, B. D. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97943 · Cited by 1,344
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Ji, R., Xu, Z., & Gao, Y. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4334 · Cited by 1,136
Resolvins and protectins in inflammation resolution
Serhan, C. N., & Petasis, N. A. (2011) · Chemical Reviews · doi:10.1021/cr100396c · Cited by 996
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Chen, G., Zhang, Y., Qadri, Y. J., Serhan, C. N., & Ji, R. (2018) · Neuron · doi:10.1016/j.neuron.2018.11.009 · Cited by 801
Metadata
- Authors
- Bazan, N. G., Calandria, J. M., & Serhan, C. N.
- Affiliations
- Louisiana State University (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Bazan, Nicolas G.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 51
- Issue
- 8
- Pages
- 2018-2031
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC2903812
- OpenAlex
- W2114448829
- Cited by
- 140
- References
- 121
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 16 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 8 · 2018: 9 · 2017: 14 · 2016: 2 · 2015: 13 · 2014: 14 · 2013: 7 · 2012: 12
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (4r37gm038765-19)
- National Eye Institute (EY005121, R01EY005121)
- National Institute of General Medical Sciences (GM 38765, R01GM038765, R37-GM038765)
- National Center for Research Resources (P20RR016816)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- neuroprotectin D1, docosahexaenoic acid, retinal pigment epithelium, retinal degeneration, phagocytosis, 15-lipoxygenase-1, neurotrophins, oxidative stress, apoptosis, anti-inflammatory signaling, polyunsaturated fatty acids
- MeSH terms
- Animals, Cell Differentiation, Docosahexaenoic Acids, Humans, Nerve Growth Factors, Photoreceptor Cells, Oxidative Stress, Retinal Pigment Epithelium
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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