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The role of renin and (pro)renin receptors in pathologic processes related to the aqueous humor outflow

Grant number: 16/09515-1
Support type:Regular Research Grants
Duration: September 01, 2016 - February 28, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Jayter Silva de Paula
Grantee:Jayter Silva de Paula
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:André Marcio Vieira Messias ; Dulce Elena Casarini ; William Daniel Stamer

Abstract

Several products related to the ischemic cascade have been associated with damage to glaucomatous targeted tissues. Cellular and extracellular changes in the trabecular meshwork (TM) and Schlemm's canal result in a routinely observed high intraocular pressure (IOP), by impacting the aqueous humor outflow. The renin-angiotensin system (RAS) has been involved in the pathological events related to ischemia and oxidative stress observed in many tissues, including the eye, but key points of this process have not been deeply studied in glaucoma. Also, considering the modulation of RAS elements has shown lowering IOP effects in humans and experimental models of glaucoma, we hypothesize that the SRA are involved in pathological changes observed in the anterior segment of patients with glaucoma. To test this hypothesis, this study will evaluate (1) the renin levels in the aqueous humor of patients with glaucoma; (2) the expression of the (pro)renin receptor and its signaling factors in cultures of TM cells; and (3) the in vitro cell viability, hydraulic conductivity, and production of fibronectin in those cultures after treatment with renin. Our findings will clarify the relationship between components of the RAS and changes in the aqueous humor outflow observed in glaucomatous eyes. In addition to the participation of graduate and postgraduate students, this study will provide innovative information, which is important for the further development of new therapeutic approaches for glaucoma, and other ocular ischemic diseases. The results will also be suitable for publication in high quality refereed journals with prominent international indexing. (AU)