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Mechanisms of retinal regeneration induction

Grant number: 12/06268-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2012
Effective date (End): May 18, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Dania Emi Hamassaki
Grantee:Carolina Beltrame Del Debbio
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The retinal degeneration, either inherited or acquired, is the leading cause of vision loss and blindness. Despite the availability of clinical treatments, these degenerations are irreversible and incurable, creating the need to develop an effective cellular regenerative therapy. The goal of this project is to promote, in situ, the reprogramming of mammalian retinal progenitor cells located in the ciliary body (CB), and to transform them into induced pluripotent cells (iPS). First, we will analyze the presence of the reprogramming machinery (expression of pluripotency genes markers: c-Myc, Oct3 / 4, Sox2 and KLF4, among others) before and after intraocular injections of growth factors. The expression and distribution of these factors will be evaluated (localization and quantification) in the cells of adult animals by immunohistochemistry, PCR and Western Blot. The next step will consist on the identification and pharmacological manipulation of possible mechanisms involved in reprogramming cells from CB, including: 1) Epigenetic mechanisms, including the analysis of the expression of methyltransferases (DNMT), effect of intraocular injections of inhibitors of DNA methyltranferases, and expression of micro RNAs (miRNA); and 2) Influence of TGF² pathway, through intraocular injections of Compound C, a chemical inhibitor of TGF² receptor types I and II, as well as activin and BMP. This study will contribute to a better understanding of the induction of iPS cells in vivo, seeking a plausible retinal regenerative therapy regardless of transplant. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre a bolsa:
Research seeks new approach to retinal repair