Neurotrophins induce neuroprotective signaling in the retinal pigment epithelial cell by activating the synthesis of the anti-inflammatory and anti-apoptotic neuroprotectin D1

Advances in Experimental Medicine and Biology
Nicolas G Bazan

Abstract

The integrity of retinal pigment epithelial cells is critical for photoreceptor cell survival and vision. The essential omega-3 fatty acid, docosahexaenoic acid, attains its highest concentration in the human body in photoreceptors. Docosahexaenoic acid is the essential precursor of neuroprotectin D1 (NPD1). NPD1 acts against apoptosis mediated by A2E, a byproduct of phototransduction that becomes toxic when it accumulates in aging retinal pigment epithelial (RPE) cells and in some inherited retinal degenerations. Here we also describe that neurotrophins, mainly pigment epithelium-derived factor, induce NPD1 synthesis and its polarized apical secretion, suggesting paracrine and autocrine bioactivity of this lipid mediator. In addition, DHA elicits a concentration-dependent and selective potentiation of pigment epithelial-derived factor-stimulated NPD1 synthesis and release through the apical RPE cell surface. The bioactivity of signaling activated by PEDF and DHA demonstrates synergistic cytoprotection when cells were challenged with oxidative stress, resulting in concomitant NPD1 synthesis. Also, DHA and PEDF synergistically activate anti-apoptotic protein expression and decreased pro-apoptotic Bcl-2 protein expression and cas...Continue Reading

Citations

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