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, including the retina, and serves as the precursor for neuroprotective and prohomeostatic 22-carbon docosanoids and 32- or 34-carbon elovanoids.
“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
Omega-3 essential fatty acid improves neurological outcomes in models of epilepsy and is neuroprotective.
“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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Alzheimer's Disease: Fatty Acids We Eat may be Linked to a Specific Protection via Low-dose Aspirin.
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- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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