Instituição onde foi realizado o trabalho
- Principal: Duke University
- Secundaria: Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (USP)
- VALERIA BATISTA BORECK SEKI (Interesse Comercial: NÃO)
- Guilherme Rabelo de Souza (Interesse Comercial: NÃO)
- Dulce Elena Casarini (Interesse Comercial: NÃO)
- William Daniel Stamer (Interesse Comercial: NÃO)
- Jayter Silva Paula (Interesse Comercial: NÃO)
A FUNCTIONAL RENIN-ANGIOTENSIN SYSTEM IN TRABECULAR MESHWORK CELLS AND AQUEOUS HUMOR OF GLAUCOMA PATIENTS.
The aqueous humor outflow resistance is regulated by a combination of factors in the trabecular meshwork (TM) and Schlemm’s canal regions. The renin-angiotensin system (RAS) may contribute to outflow resistance since modulation of some RAS enzymes decreases intraocular pressure (IOP) in experimental glaucoma. Our objective is to evaluate the effects of renin treatment on the expression of the (pro)renin receptor (PRR), TGF-beta2, connective tissue growth factor (CTGF), and beta-catenin in human TM cells cultures, as well as the levels of the angiotensin-converting enzyme (ECA) 1 and 2 levels in the aqueous humor of patients with primary open-angle glaucoma (POAG).
RNA isolated from three human TM cells strains at confluence treated with renin (10-6, 10-7, and 10-8M) in 1% FBS-low glucose DMEM for 48 h were tested using qRT-PCR for expression of PRR, TGF-beta2, CTGF, and beta-catenin. In parallel, the cellular beta-catenin localization of treated TM cells was assessed by immunofluorescence microscopy. The ECA 1 and ECA2 activities in serum and aqueous humor of POAG patients were evaluated by fluorimetric assays.
The aqueous humor of patients with POAG presented a significant increase of ECA1, but not ECA2. Immunofluorescence analysis showed a cytoplasmatic and plasma membrane distribution of beta-catenin in untreated TM cells, while beta-catenin was translocated to the nucleus in 53% of renin-treated cells. The expression of TGF-beta2 was increased, as the CTGF was decreased, in renin-treated cells, but no significant differences were observed in the renin, PRR, and beta-catenin expression.
Our results indicate a functional system for responding to renin in patients with POAG, which is related to ECA-1 activity in the aqueous humor and changes in the expression of TGF-beta2 and CTGF in TM cells. Further studies are necessary to determine additional changes in the RAS due to hypoxia and its role in the glaucomatous outflow resistance mechanisms.