Abstract
Genetic and immunohistochemical studies have identified the alternative complement pathway as an important component of age-related macular degeneration (AMD). The objective of this chapter is to review the impact of complement regulators on complement activation in the macula as it relates to AMD. Our laboratory and other investigators have identified CD46 and CD59 as important retinal pigment epithelium (RPE) cell membrane complement regulators, which are decreased in AMD. Using oxidized low-density lipoproteins (oxLDLs), which are found in Bruch’s membrane in AMD, we found that CD46 and CD59 were decreased in RPE cells in part, by their release in exosomes and apoptotic particles. The release of complement regulators could potentially impair complement regulation on RPE cells and contribute to lesion formation in the outer retina and Bruch’s membrane during the development of AMD.
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Acknowledgement
Funding: NIH EY14005 (JTH), EY019904 (JTH), Thome Foundation (JTH), AHAF (JTH), Research to Prevent Blindness Senior Scientist Award (JTH), unrestricted grant from Research to Prevent Blindness to the Wilmer Eye Institute, NIH P30EY001765 core grant, Robert Bond Welch Professorship, and a gift from the Merlau family and Aleda Wright.
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Ebrahimi, K., Fijalkowski, N., Cano, M., Handa, J. (2014). Oxidized Low-Density-Lipoprotein-Induced Injury in Retinal Pigment Epithelium Alters Expression of the Membrane Complement Regulatory Factors CD46 and CD59 through Exosomal and Apoptotic Bleb Release. 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_33
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