5. DRØFTING
5.2 V RIDNINGSEFFEKTER OG OPPMERKSOMHET
5.2.2 Prestasjonsmål
CONCLUSÕES- 45
Os resultados obtidos, nas condições propostas, permitem concluir:
1. A EIU é caracterizada pelo influxo leucocitário devido à quebra da barreira hemato-ocular, causada pela liberação de mediadores inflamatórios IL-1β, IL-6, TNF-α e NO e aumento na expressão da COX-2 nas células epiteliais e nervosas, após 24 horas da indução pelo LPS.
2. A superexpressão da COX-2, nos olhos dos camundongos deficientes para AnxA1, indica processo inflamatório exacerbado na ausência da proteína endógena.
3. Nos tecidos oculares de ratos, a expressão da AnxA1 ocorre nos epitélios da córnea, íris, processos ciliares e, também, na retina.
4. A indução da inflamação pelo LPS conduz à fosforilação da AnxA1, especificamente em serina.
5. Na EIU as expressões da AnxA1 e AnxA1-S27-PO4 são aumentadas após 24
horas da administração do LPS.
6. Os tratamentos com Ac2-26 diminuem a transmigração dos neutrófilos e reduzem os níveis de IL-1β, IL-6, TNF-α, NO e COX-2 nos tecidos oculares, após 24 horas da EIU.
7. A expressão do receptor fpr2 é mostrada pela primeira vez nos tecidos oculares e, ocorre nas mesmas regiões observadas para a AnxA1.
8. O tratamento com Ac2-26 aumenta a expressão do receptor na superfície das células endoteliais e epiteliais dos processos ciliares.
CONCLUSÕES- 46
9. A administração do antagonista Boc2 anula os efeitos anti-inflamatórios do Ac2- 26, indicando o fpr2 como receptor da AnxA1 e intermediário das ações anti- inflamatórias da proteína.
10. Os tratamentos farmacológicos, sistêmico e tópico na EIU, comprovam a potencialidade anti-inflamatória do peptídeo Ac2-26, sendo que a administração por via sistêmica apresenta os melhores resultados.
Associadas, essas conclusões mostram que a AnxA1 está envolvida na fisiologia dos tecidos oculares em condições normais e durante o estímulo inflamatório. Desse modo, os nossos resultados apontam essa proteína como alvo promissor para terapias inovadoras no tratamento de inflamações oculares, especialmente a uveíte.
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