7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Rescuing cones and daylight vision in retinitis pigmentosa mice

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hallmark of retinitis pigmentosa (RP) is the primary, genetic degeneration of rods followed by secondary loss of cones, caused by still elusive biologic mechanisms. We previously shown that exposure of rd10 mutant mice, modeling autosomal recessive RP, to environmental enrichment (EE), with enhanced motor, sensorial and social stimuli, results into a sensible delay of retinal degeneration and vision loss. Searching for effectors of EE-mediated retinal protection, we performed transcriptome analysis of the retina of rd10 enriched and control mice and found that gene expression at the peaks of rod and cone degeneration is characterized by a strong inflammatory/immune response, which is however measurably lower in enrichment conditions. Treating rd10 mice with dexamethasone during the period of maximum photoreceptors death lowered retinal inflammation and caused a preservation of cones and cone-mediated vision. Our findings indicate a link between retinal inflammation and bystander cone degeneration, reinforcing the notion that cone vision in RP can be preserved using anti-inflammatory approaches.—Guadagni, V., Biagioni, M., Novelli, E., Aretini, P., Mazzanti, C. M., Strettoi, E. Rescuing cones and daylight vision in retinitis pigmentosa mice.

          Related collections

          Most cited references44

          • Record: found
          • Abstract: found
          • Article: not found

          Brain Glucose Metabolism: Integration of Energetics with Function

          Glucose is the long-established, obligatory fuel for brain that fulfills many critical functions, including ATP production, oxidative stress management, and synthesis of neurotransmitters, neuromodulators, and structural components. Neuronal glucose oxidation exceeds that in astrocytes, but both rates increase in direct proportion to excitatory neurotransmission; signaling and metabolism are closely coupled at the local level. Exact details of neuron-astrocyte glutamate-glutamine cycling remain to be established, and the specific roles of glucose and lactate in the cellular energetics of these processes are debated. Glycolysis is preferentially upregulated during brain activation even though oxygen availability is sufficient (aerobic glycolysis). Three major pathways, glycolysis, pentose phosphate shunt, and glycogen turnover, contribute to utilization of glucose in excess of oxygen, and adrenergic regulation of aerobic glycolysis draws attention to astrocytic metabolism, particularly glycogen turnover, which has a high impact on the oxygen-carbohydrate mismatch. Aerobic glycolysis is proposed to be predominant in young children and specific brain regions, but re-evaluation of data is necessary. Shuttling of glucose- and glycogen-derived lactate from astrocytes to neurons during activation, neurotransmission, and memory consolidation are controversial topics for which alternative mechanisms are proposed. Nutritional therapy and vagus nerve stimulation are translational bridges from metabolism to clinical treatment of diverse brain disorders.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Perspective on genes and mutations causing retinitis pigmentosa.

            Exceptional progress has been made during the past two decades in identifying genes causing inherited retinal diseases such as retinitis pigmentosa. An inescapable consequence is that the relationship between genes, mutations, and clinical findings has become very complex. Success in identifying the causes of inherited retinal diseases has many implications, including a better understanding of the biological basis of vision and insights into the processes involved in retinal pathology. From a clinical point of view, there are two important questions arising from these developments: where do we stand today in finding disease-causing mutations in affected individuals, and what are the implications of this information for clinical practice? This perspective addresses these questions specifically for retinitis pigmentosa, but the observations apply generally to other forms of inherited eye disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Environment and brain plasticity: towards an endogenous pharmacotherapy.

              Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes.
                Bookmark

                Author and article information

                Journal
                FASEB J
                FASEB J
                fasebj
                fasebj
                The FASEB Journal
                Federation of American Societies for Experimental Biology (Bethesda, MD, USA )
                0892-6638
                1530-6860
                September 2019
                14 June 2019
                14 June 2019
                : 33
                : 9
                : 10177-10192
                Affiliations
                [* ]Consiglio Nazionale delle Ricerche (CNR) Institute of Neuroscience, Pisa, Italy;
                []Laboratory of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, Pisa, Italy
                Author notes
                [1]

                These authors contributed equally to this work.

                [2 ]Correspondence: Italian National Research Council (CNR), Istituto di Neuroscienze CNR, Via Giuseppe Moruzzi 1 Pisa 56124, Italy. E-mail: enrica.strettoi@ 123456in.cnr.it
                Article
                FJ_201900414R
                10.1096/fj.201900414R
                6764477
                31199887
                0edc7556-1f1a-40cc-a0ad-fe6d312d431b
                © The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 2.0 International (CC BY-NC-ND 2.0) ( https://creativecommons.org/licenses/by-nc-nd/2.0/) which permits noncommercial use, distribution, and reproduction in any medium, but prohibits the publication/distribution of derivative works, provided the original work is properly cited.

                History
                : 12 February 2019
                : 13 May 2019
                Page count
                Figures: 10, Tables: 0, Equations: 0, References: 60, Pages: 16
                Categories
                Research
                Custom metadata
                v1

                Molecular biology
                rod,bystander effect,environmental enrichment,microglia,cytokines
                Molecular biology
                rod, bystander effect, environmental enrichment, microglia, cytokines

                Comments

                Comment on this article