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      Retinal pigment epithelium and age‐related macular degeneration: A review of major disease mechanisms

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          Abstract

          Age‐related macular degeneration (AMD) is a progressive degenerative disease that is the leading cause of vision loss in the elderly population. Degeneration/dysregulation of the retinal pigment epithelium (RPE), a supportive monolayer of cells underlying the photoreceptors, is commonly seen in patients with AMD. While treatment exists for the neovascular/wet form of AMD, there is currently no cure for the non‐exudative/dry form of AMD, making it imperative to understand the pathogenesis of this disease. Although our understanding of the aetiology of AMD has increased over the years, the underlying disease mechanism has not yet been identified, mainly due to the multifactorial nature of this disease. Herein, we review some of the commonly proposed degeneration pathways of RPE cells and their role in the pathogenesis of AMD; including activation of the complement cascade, oxidative stress‐induced cell death mechanisms, dysfunctional mitochondria and the role of crystallins in AMD disease progression.

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          Most cited references116

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          Apoptosis: a review of programmed cell death.

          The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.
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            Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases.

            Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase-1, human caspase-4 and caspase-5, or mouse caspase-11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore-forming effector protein gasdermin D by inflammatory caspases. Physical rupture of the cell causes release of the pro-inflammatory cytokines IL-1β and IL-18, alarmins and endogenous danger-associated molecular patterns, signifying the inflammatory potential of pyroptosis. Here, we describe the central role of inflammatory caspases and pyroptosis in mediating immunity to infection and clearance of pathogens.
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              The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults

              The reactive oxygen species (ROS) form under normal physiological conditions and may have both beneficial and harmful role. We search the literature and current knowledge in the aspect of ROS participation in the pathogenesis of anterior and posterior eye segment diseases in adults. ROS take part in the pathogenesis of keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, stimulating apoptosis of corneal cells. ROS play a role in the pathogenesis of glaucoma stimulating apoptotic and inflammatory pathways on the level of the trabecular meshwork and promoting retinal ganglion cells apoptosis and glial dysfunction in the posterior eye segment. ROS play a role in the pathogenesis of Leber's hereditary optic neuropathy and traumatic optic neuropathy. ROS induce apoptosis of human lens epithelial cells. ROS promote apoptosis of vascular and neuronal cells and stimulate inflammation and pathological angiogenesis in the course of diabetic retinopathy. ROS are associated with the pathophysiological parainflammation and autophagy process in the course of the age-related macular degeneration.
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                Author and article information

                Contributors
                liviacarvalho@lei.org.au
                Journal
                Clin Exp Ophthalmol
                Clin Exp Ophthalmol
                10.1111/(ISSN)1442-9071
                CEO
                Clinical & Experimental Ophthalmology
                John Wiley & Sons Australia, Ltd (Melbourne )
                1442-6404
                1442-9071
                17 August 2020
                November 2020
                : 48
                : 8 , Biochemical pathways important in ocular health and disease ( doiID: 10.1111/ceo.v48.8 )
                : 1043-1056
                Affiliations
                [ 1 ] Centre for Ophthalmology and Visual Science/Lions Eye Institute University of Western Australia Nedlands Western Australia Australia
                Author notes
                [*] [* ] Correspondence

                Dr Livia S. Carvalho, University of Western Australia, Centre for Ophthalmology and Visual Science/Lions Eye Institute, 2 Verdun Street, Nedlands, WA 6009, Australia.

                Email: liviacarvalho@ 123456lei.org.au

                Author information
                https://orcid.org/0000-0002-3379-9360
                https://orcid.org/0000-0002-2140-6478
                https://orcid.org/0000-0003-3685-6516
                https://orcid.org/0000-0002-3909-5778
                Article
                CEO13834
                10.1111/ceo.13834
                7754492
                32710488
                f6810e6c-9dfa-46e5-8a93-9cc691f2c57c
                © 2020 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 February 2020
                : 05 July 2020
                : 10 July 2020
                Page count
                Figures: 3, Tables: 1, Pages: 14, Words: 11346
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                November 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:22.12.2020

                age‐related macular degeneration,apoptosis,eye,necrosis,retinal pigment epithelium

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