Satofuka Shingo, Kanda Atsuhiro, Ishida Susumu
Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan.
Front Biosci (Schol Ed). 2012 Jun 1;4(4):1449-60. doi: 10.2741/s345.
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.
受体相关的肾素原系统（RAPS）指的是肾素原与（前）肾素受体[（P）RR]结合，通过该受体双重激活组织肾素 - 血管紧张素系统（RAS）和不依赖RAS的细胞内信号传导的致病机制。尽管我们发现1型血管紧张素II受体（AT1 - R）在眼内炎症和新生血管形成（年龄相关性黄斑变性和糖尿病性视网膜病变的主要病理改变）中起重要作用，但RAPS与这些威胁视力的疾病之间的关联尚未明确。对小鼠疾病模型进行（P）RR阻断可显著抑制激光诱导的脉络膜新生血管形成和糖尿病诱导的视网膜炎症，并上调细胞间黏附分子（ICAM）-1、单核细胞趋化蛋白（MCP）-1和血管内皮生长因子（VEGF）。AT1 - R的基因敲除或药物阻断均显著减轻脉络膜和视网膜异常，而（P）RR阻断可进一步抑制这些异常。在患有视网膜和脉络膜疾病的AT1 - R缺陷小鼠中，（P）RR阻断可抑制ERK激活以及VEGF和MCP - 1的产生，但不影响ICAM - 1。这些最新发现表明RAPS在年龄相关性黄斑变性和糖尿病性视网膜病变的发病机制中起重要作用。
