Expressão de Let-7, Lin-28 e HMGA2 nas células progenitoras retinianas do epitélio ciliar de mamíferos.

Abstract

The retina is a nerve tissue that can be exposed to environmental and genetic degenerative factors, resulting in visual loss or complete blindness. Although unable to regenerate, some epithelial cells located on the retinal periphery, in the region of the Ciliary Epithelium have been identified as stem / progenitor cells capable of generating new retinal neurons. Despite its ability to regenerate retinal tissue, this capacity does not develop efficiently, indicating the presence of inhibitory mechanisms acting on the regenerative potential of Ciliary Epithelium (CE) cells. Among the currently known inhibitory mechanisms are microRNAs. In this work, we demonstrate that Let-7 family of microRNAs are highly expressed in adult mammalian CE cells, mainly in non-pigmented epithelium cells, which do not have the reprogramming capacity into stem cells. These miRNAs are poorly expressed in newborn animals and accumulate in these cells during tissue maturation / development. The proteins Lin28 and HMGA2, which are important regulators of Let-7 and one of the best described targets in the literature, respectively, showed an inverse expression pattern to Let-7, being highly expressed in newborn animals, with reduced expression with the maturation of the tissue. Ciliary epithelium cells reprogrammed into stem cells (neurospheres) showed similar Let-7 expression to newborns, with higher expression of Lin28a and Hmga2. Finally, the experimental manipulation of Let-7 by mimetic and inhibitors specific agents of this miRNA induced a significant increase of HMGA2 and a slight regulation of Lin-28, suggesting that the regulatory axis Lin-28-Let-7-HMGA may control some of the functions in the cells of the Ciliary Epithelium stem cells.