Abstract
Assembly of sub-lytic C5b-9 membrane attack complexes (MAC) on the plasma membrane of retinal pigment epithelial cells contributes to the pathogenesis of age-related macular degeneration. C5b-9 pores induce calcium influx, which activates signaling pathways that compromise cell function. Mechanisms that limit sub-lytic MAC activity include: cell surface complement regulatory proteins CD46, CD55, and CD59 that inhibit specific steps of MAC formation; elimination of assembled MAC by exocytosis of membrane vesicles or by endocytosis and subsequent lysosomal degradation; and rapid resealing of pores by the exocytosis of lysosomes. Aging in the post-mitotic retinal pigment epithelium is characterized by the accumulation of cellular debris called lipofuscin, which has also been associated with retinal diseases such as age-related macular degeneration. Lipofuscin has been shown to activate complement components both in vitro and in vivo, suggesting that it could contribute complement-mediated dysfunction in the retinal pigment epithelium. Here, we discuss emerging evidence that vesicular trafficking in the retinal pigment epithelium is critical for efficient removal of MAC from the cell surface and for limiting inflammation in the outer retina.
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Abbreviations
- AMD:
-
Age-related macular degeneration
- ESCRT:
-
Endosomal sorting complexes required for transport
- GPI:
-
Glycosylphosphatidylinositol
- MAC:
-
Membrane attack complex
- RPE:
-
Retinal pigment epithelium
- SNARE:
-
Soluble N-ethylmaleimide sensitive factor Attachment protein Receptor
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Acknowledgments
The work was supported by the American Health Assistance Foundation (M2009093), Carl Marshall and Mildred Almen Reeves Foundation, Karl Kirchgessner Foundation, Research to Prevent Blindness Career Development Award, and Retina Research Foundation Rebecca Meyer Brown Professorship.
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Lakkaraju, A., Toops, K., Xu, J. (2014). Should I Stay or Should I Go? Trafficking of Sub-Lytic MAC in the Retinal Pigment Epithelium. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_34
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DOI: https://doi.org/10.1007/978-1-4614-3209-8_34
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