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Erdal Tan Ishizuka, Atsuhiro Kanda, Yasuhiro Shinmei, Yoko Dong, Saori Inafuku, Yoshiaki Tagawa, Kousuke Noda, Susumu Ishida, ; Role of the Receptor Associated Prorenin System in Trabecular Meshwork of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3271.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is an ocular disease associated with increased intraocular pressure caused by the anatomic restriction of fluid drainage through trabecular meshwork (TM) and results in damage to the retinal neurons. The renin-angiotensin system (RAS) plays a potential role in the development of end-organ damage, and tissue RAS activation has been suggested as a risk factor for several diseases such as diabetic retinopathy. The goal of this study is to elucidate RAS and (pro)renin receptor [(P)RR]-associated pathogenesis of TM cells in glaucoma.
Surgically removed TM samples from primary open-angle glaucoma and neovascular glaucoma patients were used for immunohistochemical and immunofluorescence analyses of (P)RR and RAS components. Human TM cell lines were stimulated with angiotensin II (Ang II) or prorenin, and gene expression levels related to cell junction and extracellular matrix molecules were analyzed using real-time PCR.
(P)RR and AT1R immunoreactivities were observed in TM from patients with glaucoma and co-localized with prorenin and angiotensinogen, respectively. Gene expressions of RAS components were detected in TM cell lines by reverse transcription PCR. Real time-PCR analysis revealed that prorenin stimulation in human TM cell lines significantly upregulated mRNA expression levels of gap junction protein alpha 1 (GJA1) and tight junction protein 1 (TJP1), which were suppressed with pre-treatment of (P)RR blocker (PRRB).
Our data using clinical samples and in vitro experiments suggest that tissue RAS and (P)RR are associated with pathological events in TM of glaucoma.
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