Strong upregulation of inflammatory genes accompanies photoreceptor demise in canine models of retinal degeneration
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{"title"=>"Strong upregulation of inflammatory genes accompanies photoreceptor demise in canine models of retinal degeneration", "type"=>"journal", "authors"=>[{"first_name"=>"Tatyana", "last_name"=>"Appelbaum", "scopus_author_id"=>"57188829093"}, {"first_name"=>"Evelyn", "last_name"=>"Santana", "scopus_author_id"=>"56966377500"}, {"first_name"=>"Gustavo D.", "last_name"=>"Aguirre", "scopus_author_id"=>"56833777600"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"28486508", "sgr"=>"85019123865", "doi"=>"10.1371/journal.pone.0177224", "scopus"=>"2-s2.0-85019123865", "pui"=>"615987536", "isbn"=>"1111111111", "issn"=>"19326203"}, "id"=>"e96b9791-0191-3ffd-9c59-9f35803e034f", "abstract"=>"We have analyzed the complex pattern of the inflammatory response in early-onset canine models of human retinitis pigmentosa, rcd1, xlpra2 and erd, as well as late-onset xlpra1, in comparative manner. The time course of immune response genes and proteins expression was examined along the timeline of photoreceptors degeneration. Gene expression analysis of the early-onset models prior to and after the peak of photoreceptors death identified the involvement of multiple immune response genes including those encoding constituents of the NLRP3 inflammasome, its substrates, pro-IL1B, pro-IL18, and common components of IL1B, IL18 and TLR4 pathways. Out of two activated caspase-1 cleavage products, IL1B and IL18, only IL1B was detected in rcd1 and xlpra2 while precursor IL18 remained unpro-cessed in the same protein extract highlighting prominence of IL1B pathway. An overall immune response was most prominent in rcd1 followed by xlpra2 and least prominent in erd. Noticeably, in rcd1 and xlpra2, but not in erd, early induction of the immune response was accompanied by sustained intraretinal migration and activation of retinal microglia. Lastly, delayed activation of the anti-inflammatory factors in all early-onset models was insufficient to counterbalance rapidly progressing inflammation. In contrast to early-onset models, in late-onset xlpra1 retinas a subset of the pro-inflammatory genes was highly upre-gulated long before any disease-related structural changes occurred, but was counterbal-anced by an adequate anti-inflammatory response. Results point out to upregulated immune response accompanying disease progression in animal models of retinal degenera-tion, and to potential benefits of early anti-inflammatory therapy.", "link"=>"http://www.mendeley.com/research/strong-upregulation-inflammatory-genes-accompanies-photoreceptor-demise-canine-models-retinal-degene", "reader_count"=>8, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Other"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Other"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>1, "Veterinary Science and Veterinary Medicine"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>2}}, "group_count"=>0}

Scopus | Further Information

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