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Effects of the renin inhibitor Aliskiren on factors involved in aqueous humor outflow.

Grant number: 14/26163-6
Support Opportunities:Scholarships abroad - Research
Effective date (Start): August 01, 2015
Effective date (End): July 08, 2016
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Jayter Silva de Paula
Grantee:Jayter Silva de Paula
Host Investigator: William Daniel Stamer
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: Duke University, United States  


Glaucoma is a leading cause of blindness worldwide. Elevated intraocular pressure (IOP) is considered the main factor involving in the progression of this disease and is caused by increased aqueous humor outflow resistance. Molecular dysfunction in trabecular meshwork (TM) and Schlemm's canal (SC) cells underlie increased outflow resistance. The regulation of outflow resistance is complicated and involves a variety of local mediators, including Transforming Growth Factor-beta (TGF-beta) and Connective Tissue Growth Factor (CTGF), which modify extracellular matrix through the canonical Wnt/beta-catenin pathways. Elements of the renin-angiotensin system may also contribute to outflow resistance, since different modulators of angiotensin-converting enzymes type I and II were able to decrease IOP, through distinct actions, in humans and experimental models of glaucoma. As this system's role in resistance regulation has not been fully elucidated, we hypothesize that renin inhibitors decrease outflow resistance by inhibiting Wnt/beta-catenin signaling. To test this hypothesis we will explore the effects of aliskiren (a renin inhibitor) on (1) hydraulic conductivity of TM and SC cells; (2) aqueous humor outflow facility of mice and on (3) expression of CTGF, TGF-beta-2, fibronectin and beta-catenin by cultured outflow cells. Outcomes of the present study will define the relationship between renin-angiotensin cascade components and key points involved with the high aqueous humor outflow resistance observed in glaucoma. Future benefits of this study will be achieved with the potential implementation of renin inhibitors as new antiglaucoma agents in clinical practice.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PAULA, JAYTER S.; O'BRIEN, COIM; STAMER, W. DANIEL. Life under pressure: The role of ocular cribriform cells in preventing glaucoma. EXPERIMENTAL EYE RESEARCH, v. 151, p. 150-159, . (14/26163-6)
PAULA, JAYTER SILVA; PERKUMAS, KRISTIN; ASHPOLE, NICOLE E.; STAMER, W. DANIEL. Functional renin receptors in human Schlemm's Canal cells. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 57, n. 12, p. 2-pg., . (14/26163-6)

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