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Retinal Degenerative Diseases pp 531–540Cite as

Survival Signaling in Retinal Pigment Epithelial Cells in Response to Oxidative Stress: Significance in Retinal Degenerations

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Part of the book series: Advances in Experimental Medicine and Biology ((volume 572))

Abstract

Photoreceptor survival depends on the integrity of retinal pigment epithelial (RPE) cells. The pathophysiology of several retinal degenerations involves oxidative stress-mediated injury and RPE cell death; in some instances it has been shown that this event is mediated by A2E and its epoxides. Photoreceptor outer segments display the highest DHA content of any cell type. RPE cells are active in DHA uptake, conservation, and delivery. Delivery of DHA to photoreceptor inner segments is mediated by the interphotoreceptor matrix. DHA is necessary for photoreceptor function and at the same time is a target of oxidative stress-mediated lipid peroxidation. It has not been clear whether specific mediators generated from DHA contribute to its biological properties. Using ARPE-19 cells, we demonstrated the synthesis of 10,17S-docosatriene [neuroprotectin D1 (NPD1)]. This synthesis was enhanced by the calcium ionophore A-23187, by IL-1β, or by supplying DHA. Added NPD1 (50nM) potently counteracted H2O2/tumor necrosis factor-α oxidative stress-triggered apoptotic DNA damage in RPE. NPD1 also up-regulated the anti-apoptotic proteins Bcl-2 and Bcl-xL and decreased pro-apoptotic Bax and Bad expression. Moreover, NPD1 (50nM) inhibited oxidative stress-induced caspase-3 activation. NPD1 also inhibited IL-1β-stimulated expression of COX-2. Furthermore, A2E-triggered oxidative stress induction of RPE cell apoptosis was also attenuated by NPD1. Overall, NPD1 protected RPE cells from oxidative stress-induced apoptosis. In conclusion, we have demonstrated an additional function of the RPE: its capacity to synthesize NPD1. This new survival signaling is potentially of interest in the understanding of the pathophysiology of retinal degenerations and in exploration of new therapeutic modalities.

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Authors and Affiliations

  1. Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center School of Medicine in New Orleans, 2020 Gravier Street, Suite D, New Orleans, LA, 70112, USA

    Nicolas G. Bazan

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  1. Nicolas G. Bazan
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Editors and Affiliations

  1. Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA

    Joe G. Hollyfield

  2. Dean Mcgee Eye Institute, University of Oklahoma, Oklahoma City, OK, 73104

    Robert E. Anderson

  3. University of California, San Francisco, San Francisco, CA, 94143, USA

    Matthew M. LaVail

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Bazan, N.G. (2006). Survival Signaling in Retinal Pigment Epithelial Cells in Response to Oxidative Stress: Significance in Retinal Degenerations. In: Hollyfield, J.G., Anderson, R.E., LaVail, M.M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 572. Springer, Boston, MA. https://doi.org/10.1007/0-387-32442-9_74

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  • DOI: https://doi.org/10.1007/0-387-32442-9_74

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-28464-4

  • Online ISBN: 978-0-387-32442-5

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