FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2269968968> ?p ?o ?g. }

• W2269968968 abstract "Uveitis is the fourth leading cause of blindness in the working age population in developed countries and endogenous posterior uveoretinitis makes up 22% of the uveitis cases. The aetiology of non-infectious uveoretinitis is unknown in most cases and has been considered to have an autoimmune basis. Current treatments for autoimmune uveoretinitis are largely dependent on long-term immunosuppression with corticosteroids which can only serve to slow down the rapid progression of the disease. Similar to other autoimmune diseases, there is currently no definitive cure for autoimmune uveoretinitis and it is therefore imperative to develop more disease specific treatments with fewer side effects. Previously, combination curative strategies of bone marrow hematopoietic stem cells and gene therapy have successfully prevented and remitted the relapse of autoimmune disease in mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) which bears striking similarities to the experimental autoimmune uveoretinitis model. The overall aim of this thesis was to explore the protective effect of genetically modified bone marrow transplantation (BMT) on the development and progression of experimental autoimmune uveoretinitis.Experimental autoimmune uveoretinitis (EAU) is a widely used animal model to study human endogenous posterior uveoretinitis. The disease severity in this animal model is routinely determined by a histopathological grading method which can only be determined at a single time point. It is critical to overcome this limiting issue in order to evaluate the effectiveness of genetically modified BMT in preventing the development of EAU. Therefore, in Chapter 2, we explored the potential and reliability of using fundus images taken with a novel multi-modal imaging technique to clinically grade EAU disease severity over multiple time points. The comparison of disease severity determined by the newly derived clinical grading method and the traditional histopathology grading method showed close correlation. Furthermore, taking advantage of the multi-modal imaging system, the leukocyte profile of the normal retina and during EAU disease course was examined in transgenic mouse lines, namely the C57Bl6/J Cx3cr1GFP/+, C57Bl/6 CD11c-eYFP and C57Bl/6J LysM-eGFP mice, in which myeloid cells express the reporter fluorescent protein. Clinical examination of the fundus from naive C57Bl/6 CD11c-eYFP transgenic mice revealed multiple retinal lesions and accumulation of CD11c-eYFP+ cells. The unusual fundus appearance of naive C57Bl/6 CD11c-eYFP mice led us into suspicion of a baseline pathological status and this is investigated in Chapter 3. This study brought to the attention of eye researchers that the C57Bl/6 CD11c-eYFP mice are on a C57Bl/6N background and carry the retinal degeneration 8 (rd8) mutation in the Crumbs 1 (Crb1) gene (Chen et al. 2013). The mice with rd8 mutation displayed retinal dystrophies, in clinical and histological examination. We confirmed by genotyping that C57Bl/6 CD11c-eYFP mice were positive for the rd8 mutation and the effect of the presence of rd8 on disease severity of EAU is examined in Chapter 4. As a result of the rd8 mutation, multiple retinal lesions and an abnormal number of CD11c-eYFP+ cells were present in fundus of C57Bl/6 CD11c-eYFP mice and these were thought to contribute to development of a more severe form of EAU. However, clinical and histopathological score illustrated no difference in disease severity of EAU between C57Bl/6 CD11c-eYFP mice (with rd8 mutation) and C57Bl6/J Cx3cr1GFP/+ mice (without rd8 mutation). BMT, also known as hematopoietic stem cell transplantation, is a therapy to reconstitute the immune system with engraftment of new hematopoietic stem cells following myeloablation with total body irradiation (TBI). In Chapter 5, the effectiveness of genetically modified BMT to prevent the development of EAU in the chimeras was determined. To explore a potential combination therapy of gene therapy and BMT, haematopoietic stem cells from BM were genetically modified with lentivirus to express the retinal auto-antigen interphotoreceptor retinoid binding protein (IRBP), and red fluorescent protein (RFP). Following either lethal (1100 rads) or sub-lethal (275 rads) TBI, C57Bl/6J mice were transplanted with 0.2x106 genetically modified BM cells, expressing IRBP and RFP. The cohort of C57Bl/6J mice which received lethal TBI showed failure in engraftment and did not survive more than 2 week post-BMT with genetically modified BM cells. The failure of engraftment is suggested to be due to RFP toxicity as the issue did not occur in the control mice that received lethal TBI with non-genetically modified BM and in the mice that received sub-lethal TBI with genetically modified BM. EAU was induced at 8 week post-BMT in the chimeras that received sub-lethal TBI with genetically modified BM and the results illustrated a delayed disease onset of EAU but disease was protected only in 20% of the cohort at day 35 post-immunization. In summary, the combination therapy of gene therapy and BMT is not effective in preventing the development of EAU." @default.
• W2269968968 created "2016-06-24" @default.
• W2269968968 creator A5048851271 @default.
• W2269968968 date "2017-03-01" @default.
• W2269968968 modified "2023-09-27" @default.
• W2269968968 title "Gene therapy and bone marrow transplantation for treatment of experimental autoimmune uveoretinitis" @default.
• W2269968968 doi "https://doi.org/10.4225/03/58b649cc8b00c" @default.
• W2269968968 hasPublicationYear "2017" @default.
• W2269968968 type Work @default.
• W2269968968 sameAs 2269968968 @default.
• W2269968968 citedByCount "0" @default.
• W2269968968 crossrefType "dissertation" @default.
• W2269968968 hasAuthorship W2269968968A5048851271 @default.
• W2269968968 hasConcept C126322002 @default.
• W2269968968 hasConcept C159654299 @default.
• W2269968968 hasConcept C203014093 @default.
• W2269968968 hasConcept C2776194053 @default.
• W2269968968 hasConcept C2778486448 @default.
• W2269968968 hasConcept C2779075594 @default.
• W2269968968 hasConcept C2780007613 @default.
• W2269968968 hasConcept C2780252810 @default.
• W2269968968 hasConcept C2780640218 @default.
• W2269968968 hasConcept C2908647359 @default.
• W2269968968 hasConcept C2911091166 @default.
• W2269968968 hasConcept C71924100 @default.
• W2269968968 hasConcept C99454951 @default.
• W2269968968 hasConceptScore W2269968968C126322002 @default.
• W2269968968 hasConceptScore W2269968968C159654299 @default.
• W2269968968 hasConceptScore W2269968968C203014093 @default.
• W2269968968 hasConceptScore W2269968968C2776194053 @default.
• W2269968968 hasConceptScore W2269968968C2778486448 @default.
• W2269968968 hasConceptScore W2269968968C2779075594 @default.
• W2269968968 hasConceptScore W2269968968C2780007613 @default.
• W2269968968 hasConceptScore W2269968968C2780252810 @default.
• W2269968968 hasConceptScore W2269968968C2780640218 @default.
• W2269968968 hasConceptScore W2269968968C2908647359 @default.
• W2269968968 hasConceptScore W2269968968C2911091166 @default.
• W2269968968 hasConceptScore W2269968968C71924100 @default.
• W2269968968 hasConceptScore W2269968968C99454951 @default.
• W2269968968 hasLocation W22699689681 @default.
• W2269968968 hasOpenAccess W2269968968 @default.
• W2269968968 hasPrimaryLocation W22699689681 @default.
• W2269968968 hasRelatedWork W1499453478 @default.
• W2269968968 hasRelatedWork W1549369836 @default.
• W2269968968 hasRelatedWork W1976590223 @default.
• W2269968968 hasRelatedWork W1979659263 @default.
• W2269968968 hasRelatedWork W1992125766 @default.
• W2269968968 hasRelatedWork W2000904039 @default.
• W2269968968 hasRelatedWork W2001282809 @default.
• W2269968968 hasRelatedWork W2016535006 @default.
• W2269968968 hasRelatedWork W2037262823 @default.
• W2269968968 hasRelatedWork W2065717340 @default.
• W2269968968 hasRelatedWork W2071867810 @default.
• W2269968968 hasRelatedWork W2082983272 @default.
• W2269968968 hasRelatedWork W2101458655 @default.
• W2269968968 hasRelatedWork W2103282879 @default.
• W2269968968 hasRelatedWork W2170209911 @default.
• W2269968968 hasRelatedWork W2178116939 @default.
• W2269968968 hasRelatedWork W2396994879 @default.
• W2269968968 hasRelatedWork W2473709759 @default.
• W2269968968 hasRelatedWork W2909999815 @default.
• W2269968968 hasRelatedWork W2012840356 @default.
• W2269968968 isParatext "false" @default.
• W2269968968 isRetracted "false" @default.
• W2269968968 magId "2269968968" @default.
• W2269968968 workType "dissertation" @default.