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

Abstract

This article is available online at http://www.jlr.org RETINAL DEGENERATIVE DISEASESRetinal degenerative diseases are a complex group of conditions with different etiologies that result in a common outcome: photoreceptor apoptotic cell death ( 1-5 ). Accordingly, there are differences in how these conditions evolve. For instance, in retinitis pigmentosa (RP), rod photoreceptor death initially occurs in the periphery, whereas in age-related macular degeneration (AMD), death is initiated in the macular zone and spreads in later phases throughout the retina ( 2, 5 ). RP is a collection of inherited blinding diseases caused by the mutation of a wide variety of genes resulting in more than 150 abnormalities of photoreceptor-specifi c proteins, including mutations of rhodopsin, peripherin, the ␤ -subunit of cGMP phosphodiesterase, and retinal outer-segment membrane protein 1 ( 6-8 ).Conversely, the etiology of AMD, which is the leading cause of blindness over the age of 65, is not as clear as that of RP. AMD is also a heterogeneous group of disorders, but the causes are proposed to be multifactorial, and the main known risk factors are both genetic and environmental ( 2, 5 ). There are two forms of AMD: the dry and the wet form. In the dry form, photoreceptors degenerate slowly

Essential Role of ELOVL4 Protein in Very Long Chain Fatty Acid Synthesis and Retinal Function

“…Excessive lipofuscin in the RPE of Abca4Ϫ/Ϫ mice, a model for STGD1, appears to result from a lack of N-retinylidene-PE flippase activity of the ABCA4 protein in the disk membrane rims (39). Alternatively, it is possible that VLC-PUFAs perform a direct signaling function: Bazan et al (40) have proposed that lipid molecules, such as DHA, serve as a special class of signaling molecules that activate specific receptors. Kahn-Kirby et al (41) have reported that eicosapentaenoic acid and arachidonic acid can modulate transient receptor potential cation channel activity and modulate olfactory and nociceptive behavior.…”

Resolvins D1, D2, and Other Mediators of Self-Limited Resolution of Inflammation in Human Blood following n-3 Fatty Acid Supplementation

“…10S,17S-DiHDHA has been measured in murine peritonitis but is produced only in trace quantities by human neutrophils (24 ). PD1 has potent immunoregulatory and neuroprotective actions (25 ) and is generated by isolated human leukocytes and tissues (24 ) and in particular by neural tissues where it is referred to as NPD1 (25 ). It is antifibrotic in the kidney and promotes wound-healing capacity (8 ).…”

Dose-effect and metabolism of docosahexaenoic acid: Pathophysiological relevance in blood platelets

“…These papers have reported on several docosanoids called protectins, resolvins and maresins (reviewed in 29 & 30). One of them, protectin D1, has also been named neuroprotectin D1 because of its specific action on neuron cells (31). Based on these data, we have reconsidered the possibility of making a double lipoxygenation product of DHA able to inhibit platelet aggregation.…”