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It encodes two isoforms, namely FAIM\u2010S (short) and FAIM\u2010L (long), both with significant neuronal functions. FAIM\u2010S, which is ubiquitously expressed, is involved in neurite outgrowth. In contrast, FAIM\u2010L is expressed only in neurons and it protects them from cell death. Interestingly, FAIM\u2010L is downregulated in patients and mouse models of Alzheimer's disease before the onset of neurodegeneration, and\n                    <jats:italic>Faim<\/jats:italic>\n                    transcript levels are decreased in mouse models of retinal degeneration. However, few studies have addressed the role of FAIM in the central nervous system, yet alone the retina. The retina is a highly specialized tissue, and its degeneration has proved to precede pathological mechanisms of neurodegenerative diseases. Here we describe that\n                    <jats:italic>Faim<\/jats:italic>\n                    depletion in mice damages the retina persistently and leads to late\u2010onset photoreceptor death in older mice. Immunohistochemical analyses showed that\n                    <jats:italic>Faim<\/jats:italic>\n                    knockout (\n                    <jats:italic>Faim<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice present ubiquitinated aggregates throughout the retina from early ages. Moreover, retinal cells released stress signals that can signal to M\u00fcller cells, as shown by immunofluorescence and qRT\u2010PCR. M\u00fcller cells monitor retinal homeostasis and trigger a gliotic response in\n                    <jats:italic>Faim<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice that becomes pathogenic when sustained. In this regard, we observed pronounced vascular leakage at later ages, which may be caused by persistent inflammation. These results suggest that FAIM is an important player in the maintenance of retinal homeostasis, and they support the premise that FAIM is a plausible early marker for late photoreceptor and neuronal degeneration.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24978","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T01:15:18Z","timestamp":1635470118000},"page":"3103-3120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>Faim<\/i>\n                    knockout leads to gliosis and late\u2010onset neurodegeneration of photoreceptors in the mouse retina"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0588-0153","authenticated-orcid":false,"given":"Anna","family":"Sir\u00e9s","sequence":"first","affiliation":[{"name":"Cell Signaling and Apoptosis Group Vall d\u2019Hebron Institute of Research (VHIR)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) ISCIII  Madrid Spain"},{"name":"Departament de Bioqu\u00edmica i Biologia Molecular Facultat de Medicina Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Turch\u2010Anguera","sequence":"additional","affiliation":[{"name":"Cell Signaling and Apoptosis Group Vall d\u2019Hebron Institute of Research (VHIR)  Barcelona Spain"},{"name":"Departament de Bioqu\u00edmica i Biologia Molecular Facultat de Medicina Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra Spain"},{"name":"Diabetes and Metabolism Research Unit Vall d'Hebron Institute of Research (VHIR)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) ISCIII  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Bogdanov","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit Vall d'Hebron Institute of Research (VHIR)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) ISCIII  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Sampedro","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit Vall d'Hebron Institute of Research (VHIR)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) ISCIII  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Ramos","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit Vall d'Hebron Institute of Research (VHIR)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) ISCIII  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2633-2495","authenticated-orcid":false,"given":"Agust\u00edn","family":"Ru\u00edz Lasa","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) ISCIII  Madrid Spain"},{"name":"Research Center and Memory Clinic. Fundaci\u00f3 ACE Institut Catal\u00e0 de Neuroci\u00e8ncies Aplicades Universitat Internacional de Catalunya (UIC)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Huo","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN) A*STAR (Agency for Science, Technology and Research)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Xu","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN) A*STAR (Agency for Science, Technology and Research)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kong\u2010Peng","family":"Lam","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN) A*STAR (Agency for Science, Technology and Research)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"L\u00f3pez\u2010Soriano","sequence":"additional","affiliation":[{"name":"Cell Signaling and Apoptosis Group Vall d\u2019Hebron Institute of Research (VHIR)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) ISCIII  Madrid Spain"},{"name":"Departament de Bioqu\u00edmica i Biologia Molecular Facultat de Medicina Universitat Aut\u00f2noma de Barcelona (UAB)  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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