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Neurogenic potential of Müller glial cells: in vivo and in vitro studies

Grant number: 10/17750-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2011
Effective date (End): February 28, 2013
Field of knowledge:Health Sciences - Medicine
Principal researcher:Dania Emi Hamassaki
Grantee:Cristiano Neiva Pessôa
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Evidences that Müller glial cells generate new neurons in response to injury suggest that they are a potential source for retinal regeneration. Although limited, a regenerative program occurs in mammals and could be useful to develop new therapies for treating patients with retinal degeneration. The present project aims to investigate by in vitro and in vivo studies the Müller glial cells dedifferentiation and neuronal differentiation of both chicken and rat, which show distinct regenerative responses to injury. Specifically, we will investigate some Rho GTPases, proteins that were previously described in Müller cells by our group, and which regulate multiple signaling pathways, including those related to proliferation and differentiation, such as Notch and Wnt. Müller cell cultures and neurospheres will be treated with Rho GTPases inhibitors or activators and different markers for neural and glial progenitor cells, differentiated cells and Notch and Wnt pathways will be analyzed by real-time PCR and immunofluorescence. In some cases lentivirus carrying the shRNA to silence some of these GTPases will be used. The most significant in vitro results will be also investigated in vivo after retinal damage by N-Methyl-D-aspartate and treatment with Rho GTPases inhibitors. Our results may contribute to better understand the factors that influence the regenerative process, as well as may provide a basis to develop new strategies to treat retinal and other CNS degenerative diseases. (AU)