Abstract
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.
Highlights
Retinal degenerative diseases result in retinal pigment epithelial (RPE) and photoreceptor cell loss
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]
The increased availability of docosahexaenoic acid (DHA) is followed by neuroprotectin D1 (NPD1) synthesis. This is of particular interest in the process of phagocytosis of photoreceptor outer segments, given that the endogenous pool of DHA is augmented upon activation of the RPE cell phagolysosomal system
Summary
Retinal degenerative diseases are a complex group of conditions with different etiologies that result in a common outcome: photoreceptor apoptotic cell death [1,2,3,4,5]. The presence of oxidative damage markers in postmortem retinas of patients with geographic atrophy shows, at least in the dry form, oxidative stress is involved in the pathogenic mechanisms of AMD [11] In this manner, oxidative stress is enhanced and exaggerated and mitochondrial function is compromised [8,9,10,11,12,13], which leads to apoptotic cell death. Tunel studies performed on postmortem human retinas of patients presenting geographic atrophy and exudative forms of the disease show that apoptosis is the main mechanism of degeneration, for photoreceptors, and for the RPE and inner retinal layers [12]. The identification of early pro-survival, antiinflammatory signaling critical for the maintenance of photoreceptor cell integrity may be applicable for novel therapeutic intervention/s for slowing or halting disease progression
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