Involvement of microRNAs in alterations of the vitreoretinal interface

Abstract

Population aging leads to an increase in the incidence of complications arising from changes in the vitreoretinal interface and that can cause vision loss. In part, this is due to the remodeling of vitreous, a highly hydrated extracellular matrix predominantly composed of hyaluronic acid, collagen types II, V / XI and IX and rare cells called hyalocytes. With age, the vitreous undergoes a series of molecular and structural modifications that result in liquefaction. As a consequence, other complications may arise, such as retinal detachment and rupture, among others, causing vision loss. Our aim is to investigate factors that could regulate these processes, by studying expression and role of miRNAs in the aging vitreous and retina, as well as in some diseases of the vitreoretinal interface. MicroRNAs (miRNAs) are small non-coding RNAs that act on specific RNAs by regulating gene expression and participating in the control of relevant signaling pathways involved in various diseases. The miRNAs potential as molecular markers have been widely investigated in recent years, but the biological role of these molecules remains unclear. In this context, miRNAs of let-7 family control multiple targets involved in cell proliferation and differentiation, appear to have a role in senescence and have various components of the extracellular as predicted targets. Specifically, we will investigate: 1) Expression of miRNAs in the rat retina and vitreous of neonates, adults and aging; 2) Possible sources of these miRNAs in the vitreous (Müller glial cells, ciliary body, hyalocytes and blood); 3) miRNAs expression in human vitreous samples from diagnosed vitreoretinal diseases (epiretinal membranes, macular hole and rhegmatogenous retinal detachment) collected during vitrectomy surgery via pars plana and from control eyes obtained from an Eye Bank; 4) Influence of human vitreous samples from different regions and diagnostics on the activity of potential target cells in vitro (hyalocytes, Müller and ciliary epithelium cells); 5) the functional role of the most important miRNAs through overexpression and inhibition of the potential target cells in vitro (hyalocytes, Müller cells and ciliary epithelium cells).The results should contribute to a better understanding of the processes that occur during aging and some diseases of the vitreoretinal interface, as well as for the development of future therapeutic approaches. (AU)