title: Inflammation and Cell Death in Age-Related Macular Degeneration: An Immunopathological and Ultrastructural Model.
abstract: The etiology of Age-related Macular Degeneration (AMD) remains elusive despite the characterization of many factors contributing to the disease in its late-stage phenotypes. AMD features an immune system in flux, as shown by changes in macrophage polarization with age, expression of cytokines and complement, microglial accumulation with age, etc. These point to an allostatic overload, possibly due to a breakdown in self vs. non-self when endogenous compounds and structures acquire the appearance of non-self over time. The result is inflammation and inflammation-mediated cell death. While it is clear that these processes ultimately result in degeneration of retinal pigment epithelium and photoreceptor, the prevalent type of cell death contributing to the various phenotypes is unknown. Both molecular studies as well as ultrastructural pathology suggest pyroptosis, and perhaps necroptosis, are the predominant mechanisms of cell death at play, with only minimal evidence for apoptosis. Herein, we attempt to reconcile those factors identified by experimental AMD models and integrate these data with pathology observed under the electron microscope-particularly observations of mitochondrial dysfunction, DNA leakage, autophagy, and cell death.
authors.affiliation: Histology Core, Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland 20892-1857, MD, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Ardeljan
authors.affiliation: Human Genetics Program, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, MD, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ardeljan
authors.affiliation: Histology Core, Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland 20892-1857, MD, USA.
authors.forename: Mones
authors.initials: M
authors.lastname: Abu-Asab
authors.affiliation: Histology Core, Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland 20892-1857, MD, USA ; Immunopathology Section, Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland 20892-1857, MD, USA.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
keywords: age-related macular degeneration (AMD); apoptosis; autophagy; cytokine; inflammasome; macrophage; microglia; necroptosis; pyroptosis