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      IGF-1, Inflammation and Retinal Degeneration: A Close Network

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          Abstract

          Retinal degenerative diseases are a group of heterogeneous diseases that include age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). The progressive degeneration of the retinal neurons results in a severe deterioration of the visual function. Neuroinflammation is an early hallmark of many neurodegenerative disorders of the retina including AMD, RP and DR. Microglial cells, key components of the retinal immune defense system, are activated in retinal degenerative diseases. In the microglia the interplay between the proinflammatory/classically activated or antiinflammatory/alternatively activated phenotypes is a complex dynamic process that occurs during the course of disease due to the different environmental signals related to pathophysiological conditions. In this regard, an adequate transition from the proinflammatory to the anti-inflammatory response is necessary to counteract retinal neurodegeneration and its subsequent damage that leads to the loss of visual function. Insulin like-growth factor-1 (IGF-1) has been considered as a pleiotropic factor in the retina under health or disease conditions and several effects of IGF-1 in retinal immune modulation have been described. In this review, we provide recent insights of inflammation as a common feature of retinal diseases (AMD, RP and RD) highlighting the role of microglia, exosomes and IGF-1 in this process.

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          Microglia development and function.

          Proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of parenchymal sentinels referred to as microglia. Although microglia were first described as ramified brain-resident phagocytes, research conducted over the past century has expanded considerably upon this narrow view and ascribed many functions to these dynamic CNS inhabitants. Microglia are now considered among the most versatile cells in the body, possessing the capacity to morphologically and functionally adapt to their ever-changing surroundings. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Microglia are in fact vital participants in CNS homeostasis, and dysregulation of these sentinels can give rise to neurological disease. In this review, we discuss the exciting developments in our understanding of microglial biology, from their developmental origin to their participation in CNS homeostasis and pathophysiological states such as neuropsychiatric disorders, neurodegeneration, sterile injury responses, and infectious diseases. We also delve into the world of microglial dynamics recently uncovered using real-time imaging techniques.
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            Retinal microglia: just bystander or target for therapy?

            Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human tissue that microglial reactivity is a common hallmark of various retinal degenerative and inflammatory diseases. These include rare hereditary retinopathies such as retinitis pigmentosa and X-linked juvenile retinoschisis but also comprise more common multifactorial retinal diseases such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis as well as neurological disorders with ocular manifestation. In this review, we describe how microglial function is kept in balance under normal conditions by cross-talk with other retinal cells and summarize how microglia respond to different forms of retinal injury. In addition, we present the concept that microglia play a key role in local regulation of complement in the retina and specify aspects of microglial aging relevant for chronic inflammatory processes in the retina. We conclude that this resident immune cell of the retina cannot be simply regarded as bystander of disease but may instead be a potential therapeutic target to be modulated in the treatment of degenerative and inflammatory diseases of the retina.
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              Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene.

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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                05 July 2018
                2018
                : 10
                : 203
                Affiliations
                [1] 1Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM) , Madrid, Spain
                [2] 2Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII , Madrid, Spain
                [3] 3Research Unit, Instituto de Investigación e Innovación en Ciencias Biomédicas de la Provincia de Cádiz (INiBICA), University Hospital “Puerta del Mar” , Cádiz, Spain
                [4] 4Department of Endocrinology and Metabolism, Instituto de Investigación e Innovación en Ciencias Biomédicas de la Provincia de Cádiz (INiBICA), University Hospital “Puerta del Mar” , Cádiz, Spain
                Author notes

                Edited by: Luis Miguel Garcia-Segura, Consejo Superior de Investigaciones Científicas (CSIC), Spain

                Reviewed by: Thomas Langmann, Lehrstuhl für Experimentelle Immunologie des Auges, Medizinische Fakultät, Universität zu Köln, Germany; Jose L. Labandeira-Garcia, Universidade de Santiago de Compostela, Spain

                *Correspondence: Ana I. Arroba anaarroba@ 123456gmail.com
                Ángela M. Valverde avalverde@ 123456iib.uam.es

                †Present Address: Ana I. Arroba, Research Unit, Instituto Investigación e Innovación Biomédica de Cádiz (INIBICA), University Hospital “Puerta del Mar”, Cádiz, Spain

                Article
                10.3389/fnagi.2018.00203
                6041402
                30026694
                df6261d4-f1b6-4846-8f19-0788c936165c
                Copyright © 2018 Arroba, Campos-Caro, Aguilar-Diosdado and Valverde.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 April 2018
                : 14 June 2018
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 139, Pages: 12, Words: 10960
                Categories
                Neuroscience
                Review

                Neurosciences
                retina,inflammation,neurodegeneration,igf-1,microglia and exosomes
                Neurosciences
                retina, inflammation, neurodegeneration, igf-1, microglia and exosomes

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