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Studium imunopatologických mechanismů autoimunitní uveitidy a definování nových terapeutických možností.
Název práce v češtině: Studium imunopatologických mechanismů autoimunitní uveitidy a definování nových terapeutických možností.
Název v anglickém jazyce: Study of immunopathological mechanisms of autoimmune uveitis and the determination of new therapeutical options.
Klíčová slova: antibiotika, bezmikrobní model, ciprofloxacin, cyklofosfamid, cytokiny, experimentální autoimunitní uveitida, C57BL/6, metronidazol, mikrobiota, mikrobiom, mykofenolát mofetil, nitrooční tekutina
Klíčová slova anglicky: antibiotics, germ-free model, ciprofloxacin, cyclophosphamide, cytokines, experimental autoimmune uveitis, C57BL/6, metronidazole, microbiota, microbiome, mycophenolate mofetil, intraocular fluid
Akademický rok vypsání: 2013/2014
Typ práce: disertační práce
Jazyk práce: čeština
Ústav: Oční klinika 1. LF UK a VFN (11-00750)
Vedoucí / školitel: prof. MUDr. Petra Svozílková, Ph.D.
Řešitel: skrytý - zadáno a potvrzeno stud. odd.
Datum přihlášení: 31.07.2014
Datum zadání: 31.07.2014
Datum potvrzení stud. oddělením: 31.07.2014
Datum a čas obhajoby: 17.06.2020 15:00
Místo konání obhajoby: v seminární místnosti č. 4, 1. patro, Farmakologického ústavu, 1. LF UK a VFN, Albertov 4, Praha 2.
Datum odevzdání elektronické podoby:28.02.2020
Datum proběhlé obhajoby: 17.06.2020
Předmět: Obhajoba dizertační práce (B90002)
Oponenti: prof. MUDr. Pavel Rozsíval, CSc.
  prof. Dr. Hassan Farghali, DrSc.
 
 
Konzultanti: prof. MUDr. Jarmila Heissigerová, Ph.D., MBA
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Předběžná náplň práce
Cílem této práce bylo získat nové poznatky o mechanismech autoimunitní uveitidy a testovat nové způsoby léčby, které nebyly u uveitid studovány nebo jejichž efekt je sporný. Hlavní důraz byl kladen na úlohu mikroorganismů v procesu uveitidy.
K dosažení cílů byl využit myší model experimentální autoimunitní uveitidy včetně modelu bezmikrobního a byly analyzovány vzorky nitroočních tekutin pacientů. Na experimentálním modelu byla hodnocena intenzita zánětu in vivo klinicky a post mortem histologicky. Hodnocen byl efekt imunomodulační léčby. Intenzita zánětu byla porovnána mezi skupinami bezmikrobních a konvenčních myší. U konvenčních myší byl sledován terapeutický efekt antibiotik podávaných s cílem ovlivnit mikrobiom. Ve vzorcích nitroočních tekutin pacientů s autoimunitní uveitidou byly sledovány známky po proběhlém infekčním procesu a hodnoceny hladiny cytokinů a dalších faktorů.
Zhodnocení efektu imunomodulační léčby prokázalo účinnost mykofenolát mofetilu, což podporuje jeho širší využití při léčbě autoimunitní zadní uveitidy v humánní medicíně. Snížení bakteriálního osídlení vedlo k poklesu intenzity zánětu, a tím potvrdilo význam mikroorganismů v procesu autoimunitní uveitidy, a to jak u bezmikrobních myší, tak u konvenčních myší léčených antibiotiky. Výsledky analýzy nitroočních tekutin podporují hypotézu o vlivu infekce při vzniku autoimunitní uveitidy.
Získané výsledky by mohly iniciovat další výzkum v této oblasti a dospět k cílené regulaci faktorů vyvolávajících autoimunitní uveitidu, a tím snížit procento slepoty vzniklé následkem uveitidy.
Předběžná náplň práce v anglickém jazyce
The aim of this work was to gain new knowledge about mechanisms of autoimmune uveitis and to test new therapeutic possibilities that have not yet been studied in uveitis or whose effect is questionable. The main emphasis was placed on the role of microorganisms in the process of uveitis.
A mouse model of experimental autoimmune uveitis including a germ-free model was used to achieve the aims and samples of patients' intraocular fluids were analyzed. In the experimental model, the intensity of inflammation was evaluated in vivo clinically and post mortem histologically. The effect of immunomodulatory treatment was evaluated. The intensity of inflammation was compared between groups of germ-free and conventional mice. The therapeutic effect of antibiotics administered to affect microbiome was investigated in conventional mice. In intraocular fluid samples of patients with autoimmune uveitis signs of infection were monitored and levels of cytokines and other factors were evaluated.
Evaluation of the effect of immunomodulatory therapy has demonstrated the efficacy of mycophenolate mofetil, which supports its wider use in the treatment of autoimmune posterior uveitis in human medicine. The decrease in bacterial load has led to a decrease in the intensity of inflammation, thereby confirming the importance of microorganisms in the process of autoimmune uveitis in both germ-free and conventional antibiotic-treated mice. The results of intraocular fluid analysis support the hypothesis of the effect of infection on the induction of autoimmune uveitis.
The results obtained could initiate further research in this area and achieve a targeted regulation of the factors causing autoimmune uveitis, thereby reducing the percentage of blindness due to uveitis.
 
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