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      The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut–Retina Axis

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          Abstract

          Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30–50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

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          Most cited references120

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          Prevalence of age-related macular degeneration in the United States.

          To estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender. Summary prevalence estimates of drusen 125 microm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD. The overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval, 1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 microm or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons. Age-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.
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            The gut microbiota and inflammatory bowel disease

            Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut. Although the precise cause of IBD remains unknown, the most accepted hypothesis of IBD pathogenesis to date is that an aberrant immune response against the gut microbiota is triggered by environmental factors in a genetically susceptible host. The advancement of next-generation sequencing technology has enabled identification of various alterations of the gut microbiota composition in IBD. While some results related to dysbiosis in IBD are different between studies owing to variations of sample type, method of investigation, patient profiles, and medication, the most consistent observation in IBD is reduced bacterial diversity, a decrease of Firmicutes, and an increase of Proteobacteria. It has not yet been established how dysbiosis contributes to intestinal inflammation. Many of the known IBD susceptibility genes are associated with recognition and processing of bacteria, which is consistent with a role of the gut microbiota in the pathogenesis of IBD. A number of trials have shown that therapies correcting dysbiosis, including fecal microbiota transplantation and probiotics, are promising in IBD.
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              A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss

              (2001)
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                05 November 2018
                November 2018
                : 10
                : 11
                : 1677
                Affiliations
                [1 ]UOC di Nutrizione Clinica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; emanuele.rinninella@ 123456unicatt.it (E.R.); gaia.anselmi@ 123456gmail.com (G.A.); antonio.gasbarrini@ 123456unicatt.it (A.G.)
                [2 ]Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
                [3 ]Laboratorio di Nutrizione Cellulare e Molecolare, Dipartimento di Scienze Ecologiche e Biologiche (DEB), Università della Tuscia, Largo dell’Università snc, 01100 Viterbo, Italy; merendin@ 123456unitus.it
                [4 ]Scuola di Specializzazione in Scienza dell’Alimentazione, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; marco.cintoni@ 123456gmail.com
                [5 ]UOC di Oculistica, Dipartimento di Scienze dell’Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; aldo.caporossi@ 123456unicatt.it (A.C.); angelomaria.minnella@ 123456unicatt.it (A.M.M.)
                [6 ]Istituto di Oftalmologia, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
                Author notes
                [* ]Correspondence: mariacristina.mele@ 123456unicatt.it ; Tel.: +39-06-3015-6018
                Author information
                https://orcid.org/0000-0002-9165-2367
                https://orcid.org/0000-0001-5044-1398
                https://orcid.org/0000-0002-9610-0748
                https://orcid.org/0000-0001-5896-5313
                Article
                nutrients-10-01677
                10.3390/nu10111677
                6267253
                30400586
                db47d234-fdcb-4389-8148-f6ef8e692cb8
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 October 2018
                : 31 October 2018
                Categories
                Review

                Nutrition & Dietetics
                age-related macular degeneration,gut-retina axis,gut microbiota,dietary habits,micronutrients,fish oil,omega-3 polyunsaturated fatty acids,personalised medicine

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