{"doi":"10.1073/pnas.1620299114","title":"Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>The complement system, a key component of innate immunity, is necessary to maintain tissue homeostasis. In the eye, the retinal pigment epithelium (RPE) plays a major role in controlling the immune response through expression of various complement negative regulatory proteins (CRPs). Here we identify that inappropriate activation of the complement cascade plays a role in the pathogenesis of recessive Stargardt disease (STGD1). Using the STGD1 mouse model, we show that overexpression of the complement receptor 1-like protein y, a major murine CRP, reduces complement attack on the RPE and rescues both bisretinoid accumulation and photoreceptor degeneration. Our data demonstrate that STGD1 presents with dysregulation of the complement system as also has been proposed for age-related macular degeneration, supporting a common etiologic pathway.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2017,"id":646614,"datarank":0.6329261557764161,"base_score":4.219507705176107,"endowment":4.219507705176107,"self_citation_contribution":0.6329261557764161,"citation_network_contribution":0.0,"self_endowment_contribution":0.6329261557764161,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":505873,"name":"Shanta Sarfare","orcid":null,"position":1,"is_corresponding":false},{"id":365822,"name":"Zhichun Jiang","orcid":null,"position":2,"is_corresponding":false},{"id":1684341,"name":"Marcia B. Lloyd","orcid":null,"position":3,"is_corresponding":false},{"id":872117,"name":"Dean Bok","orcid":null,"position":4,"is_corresponding":false},{"id":364888,"name":"Roxana A. Radu","orcid":"0000-0002-5064-6403","position":5,"is_corresponding":false},{"id":1684340,"name":"Tamara L. Lenis","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>The complement system, a key component of innate immunity, is necessary to maintain tissue homeostasis. In the eye, the retinal pigment epithelium (RPE) plays a major role in controlling the immune response through expression of various complement negative regulatory proteins (CRPs). Here we identify that inappropriate activation of the complement cascade plays a role in the pathogenesis of recessive Stargardt disease (STGD1). Using the STGD1 mouse model, we show that overexpression of the complement receptor 1-like protein y, a major murine CRP, reduces complement attack on the RPE and rescues both bisretinoid accumulation and photoreceptor degeneration. Our data demonstrate that STGD1 presents with dysregulation of the complement system as also has been proposed for age-related macular degeneration, supporting a common etiologic pathway.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28348233","pmcid":"PMC5393232","openalex_id":"https://openalex.org/W28348233","authors":[],"funders":[{"funder_name":"HHS | NIH | National Eye Institute","grant_id":"EY000331","title":null},{"funder_name":"HHS | NIH | National Eye Institute","grant_id":"EY025002","title":null},{"funder_name":"NEI NIH HHS","grant_id":"P30 EY000331","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY025002","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01EY025002-05","title":"The Role of Complement in Recessive Stargardt Disease"}],"total_grants":5,"fwci":0.0,"citation_percentile":0.01423639,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"cc-by","oa_locations":[{"url":"https://dialnet.unirioja.es/servlet/articulo?codigo=2143723","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/114/15/3987.full.pdf","host_type":"publisher"},{"url":"http://www.pnas.org/syndication/doi/10.1073/pnas.1620299114","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1620299114","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1620299114","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/28348233","host_type":""},{"url":"https://dx.doi.org/10.1073/pnas.1620299114","host_type":""},{"url":"https://escholarship.org/uc/item/8zg5q4r3","host_type":""},{"url":"https://escholarship.org/uc/item/8678m6cs","host_type":""},{"url":"https://doi.org/https://doi.org/10.1073/pnas.1620299114","host_type":""}],"fields_of_study":["Media, Journalism, and Communication History","History of Education in Spain","Spanish Literature and Culture Studies","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Animals","Mice, Inbred BALB C","Mice, Mutant Strains","Dependovirus","Macular Degeneration","Disease Models, Animal","Retinoids","Lipofuscin","ATP-Binding Cassette Transporters","Receptors, Complement","Receptors, Complement 3b","Gene Expression Regulation","Oxidative Stress","Autophagy","Complement C3","Photoreceptor Cells, Vertebrate","Retinal Pigment Epithelium","Injections, Intraocular","Stargardt Disease"],"keywords":["Art","Humanities","Gene therapy","Complement system","retinal pigment epithelium","Bisretinoids","Recessive Stargardt Macular Degeneration","Complement","Neurodegenerative","Eye","Injections","Lipofuscin","Mice","Macular Degeneration","Retinoids","Rare Diseases","Receptors","Genetics","Autophagy","Animals","Stargardt Disease","Photoreceptor Cells","Eye Disease and Disorders of Vision","Inbred BALB C","Mice, Inbred BALB C","Animal","Vertebrate","Intraocular","Neurosciences","Complement C3","Complement 3b","Dependovirus","Mice, Mutant Strains","Receptors, Complement","Mutant Strains","Disease Models, Animal","Oxidative Stress","Gene Expression Regulation","Disease Models","Receptors, Complement 3b","ATP-Binding Cassette Transporters","Injections, Intraocular","Biotechnology","Photoreceptor Cells, Vertebrate"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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