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O Corpo Ciliar (CC) e uma fonte de celulas tronco da retina de animais adultos, mas sua ativacao permanece desconhecida. GTPases Rho sao proteinas que reorganizam do citoesqueleto de actina, regulam vias de sinalizacao e transcricao genica, sobrevivencia celular e proliferacao. Neste trabalho, investigamos a expressao das GTPases Rho nas celulas do CC e seu efeito na regulacao do ciclo celular. As GTPases RhoA, RhoB e Rac1 foram expressas nas celulas do CC e sua ativacao pelo acido lisofosfatidico (LPA) aumentou a expressao dos genes progenitores retinianos Pax6 e Chx10. A inibicao das proteinas por Toxina A de Clostridium difficile aumentou a proliferacao no CC e potencializou o efeito proliferativo dos fatores de crescimento. A inibicao especifica destas proteinas diminuiu a expressao dos transcritos de p21cip, p27kip, p16INK4a e p19INK4d e aumentou de Ki67, CiclinaA e D1. O estudo da via de Wnt indicou que Rac1 regulou os genes de componentes da degradacao de -catenina e Lef1. Concluimos que a inativacao das GTPases Rho induziu a proliferacao das celulas progenitoras retinianas localizadas no CC e regulou a via de Wnt. Sua ativacao induziu o perfil de celula progenitora, sugerindo uma nova ferramenta para o mecanismo de reparo retiniano.%%%%Ciliary Body (CB) is a potential source of stem cells in the adult retina, but its activation is still unknown. Rho GTPases play a role in actin-based cytoskeleton reorganization, regulate signaling pathways and gene transcription, cell survival and cell proliferation. In this study we investigated the expression of Rho GTPases in CB cells and their role on cell cycle regulation. The GTPases RhoA, RhoB and Rac1 were present in CB cells and the activation by lysophosphatidic acid (LPA) increased the expression of the progenitor genes Pax6 and Chx10. The inhibition by Clostridium difficile Toxin A increased the proliferation of CB cells and potentiated the proliferative effect of growth factors. The specific inhibition decreased the expression of p21cip, p27kip, p16INK4a and p19INK4d as well as increased Ki67, cyclinA and D1 transcripts. The Wnt pathway study indicated that Rac1 regulated -catenin degradation genes components and Lef1. Taken together, the inactivation of Rho GTPases stimulated the proliferation of progenitor cells located in CB as well as regulate the Wnt signaling pathway. The proteins activation was correlated to progenitor profile induction. These different mechanisms may provide a potential new approach on retinal repair.

GTPases Rho e o potencial regenerativo da retina de mamíferos