IMR Press / FBS / Volume 4 / Issue 4 / DOI: 10.2741/S345

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Receptor-associated prorenin system in the pathogenesis of retinal diseases
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1 Department of Ophthalmology, Teikyo University School of Medicine, Tokyo 173-8605, Japan
2 Laboratory of Retinal Cell Biology, Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan
3 Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan

*Author to whom correspondence should be addressed.

 

Front. Biosci. (Schol Ed) 2012, 4(4), 1449–1460; https://doi.org/10.2741/S345
Published: 1 June 2012
Abstract

Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanisms whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling through the receptor. Although we found significant involvement of angiotensin II type 1 receptor (AT1-R) in intraocular inflammation and neovascularization, central pathologies of age-related macular degeneration and diabetic retinopathy, the association of RAPS with these vision-threatening disorders has not been defined. (P)RR blockade to murine disease models led to significant suppression of laser-induced choroidal neovascularization and diabetes-induced retinal inflammation together with the upregulation of intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1 and vascular endothelial growth factor (VEGF). Either the genetic ablation or the pharmacological blockade of AT1-R exhibited significant reduction of choroidal and retinal abnormalities, both of which were further suppressed by (P)RR blockade. (P)RR blockade inhibited ERK activation and the production of VEGF and MCP-1, but not ICAM-1, in AT1-R-deficient mice with retinal and choroidal disorders. These recent findings indicate significant contribution of RAPS to the pathogenesis of age-related macular degeneration and diabetic retinopathy.

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