Related Experiment Video

Updated: Jun 28, 2026

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
12:03

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors

Published on: June 7, 2016

(Pro)renin receptor promotes choroidal neovascularization by activating its signal transduction and tissue

Shingo Satofuka1, Atsuhiro Ichihara, Norihiro Nagai

  • 1Laboratory of Retinal Cell Biology, Inaida Endowed Department of Anti-Aging Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

The American Journal of Pathology
|November 1, 2008
PubMed

Insights

The receptor-associated prorenin system (RAPS) significantly contributes to choroidal neovascularization (CNV). Blocking the (pro)renin receptor suppressed CNV and related inflammatory markers, highlighting RAPS as a therapeutic target for vision-threatening conditions.

Area of Science:

  • Ophthalmology
  • Cardiovascular Biology
  • Cell Signaling

Background:

  • The receptor-associated prorenin system (RAPS) involves prorenin binding to its receptor, activating tissue renin-angiotensin system (RAS) and RAS-independent pathways.
  • Choroidal neovascularization (CNV), a key feature of age-related macular degeneration, involves inflammation mediated by angiotensin II type 1 receptor (AT1-R).
  • The specific role of RAPS in CNV pathogenesis remained undefined.

Purpose of the Study:

  • To investigate the association of the receptor-associated prorenin system (RAPS) with choroidal neovascularization (CNV).
  • To elucidate the role of signal transduction via the (pro)renin receptor in CNV development.
  • To assess the therapeutic potential of (pro)renin receptor blockade in a murine model of CNV.

Main Methods:

  • Laser-induced CNV model in mice.
  • Pharmacological blockade of AT1-R with losartan and genetic ablation of AT1-R or angiotensinogen to deactivate the RAS.
  • Assessment of CNV volume, macrophage infiltration, and expression of inflammatory markers (ICAM-1, MCP-1, VEGF, VEGFR-1, VEGFR-2) and ERK activation.

Main Results:

  • (Pro)renin receptor blockade significantly suppressed CNV, macrophage infiltration, and the expression of ICAM-1, MCP-1, VEGF, VEGFR-1, and VEGFR-2 in a murine CNV model.
  • Mice with deactivated RAS (losartan-treated or genetically modified) showed reduced CNV and macrophage infiltration, further suppressed by (pro)renin receptor blockade.
  • (Pro)renin receptor blockade inhibited ERK activation and MCP-1 and VEGF production in AT1-R-deficient conditions, indicating a RAPS-specific effect.

Conclusions:

  • The receptor-associated prorenin system (RAPS) significantly contributes to the pathogenesis of choroidal neovascularization (CNV).
  • (Pro)renin receptor blockade effectively suppresses CNV and associated inflammatory processes.
  • RAPS represents a potential therapeutic target for treating CNV and related vision-threatening diseases.

More Related Videos

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis08:21

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis

Published on: October 26, 2020

Related Concept Videos

Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Hormonal Regulation01:33

Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
Hypertension II: Pathophysiology01:29

Hypertension II: Pathophysiology

Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...