Rescue and repair during photoreceptor cell renewal mediated by docosahexaenoic acid-derived neuroprotectin D1

Department of Ophthalmology, School of Medicine, Louisiana State University Health Sciences Center, Neuroscience Center of Excellence, New Orleans, LA 70112, USA.
The Journal of Lipid Research (Impact Factor: 4.42). 04/2010; 51(8):2018-31. DOI: 10.1194/jlr.R001131
Source: PubMed


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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    • "acute inflammatory responses) are programmed to be self-limited and tightly controlled [8] [9] [10]. Lipid mediators such as prostaglandins and leukotrienes play pivotal roles in the initiation of acute inflammation [11], whereas resolvins and protectins promote and stimulate active resolution [8] [9] [12]. In excess, prostaglandins and leukotrienes are generally pro-inflammatory [11] and involved in the classic initiation phase of the acute inflammatory response in humans. "
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    Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 08/2014; 1851(4). DOI:10.1016/j.bbalip.2014.08.006 · 5.16 Impact Factor
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    • "These data indicate tight regulation of DHA homeostasis in RPE cells. The DHA-derived compounds, protectin D1, neuroprotectin D1 and resolvin D1, have been identified as anti-inflammatory lipid mediators (Bazan et al., 2010; Mukherjee et al., 2004; Serhan et al., 2004). Therefore, the well-recognized role of CYP4 enzymes in fatty acid metabolism and the suspected abnormal lipid metabolism in BCD raises the possibility that a deficiency in the PUFAhydroxylase catalytic function of CYP4V2 might play a role in BCD (Kelly et al., 2011). "
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    Drug Metabolism Reviews 05/2014; 46(3):1-14. DOI:10.3109/03602532.2014.921190 · 5.36 Impact Factor
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    • "To replace the damaged outer segments, photoreceptors shed the distal tips of the outer segments, which are phagocytosed by retinal pigment epithelial (RPE) cells. RPE cells respond to oxidative stress by synthesizing protectin D1 from DHA in the phagocytosed outer segment membranes (Bazan et al., 2010). Protectin D1 promotes the survival of RPE cells, and, as a consequence, photoreceptor cell integrity (Mukherjee et al., 2007). "
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