Suppression of Ocular Inflammation in Endotoxin-Induced Uveitis by Inhibiting Nonproteolytic Activation of Prorenin

Abstract

These findings demonstrate for the first time that nonproteolytically activated prorenin plays a significant role in the development of ocular inflammation in the EIU model. The present study suggests the potential use of HRP, a decoy peptide binding to the prorenin receptor, as a therapeutic agent to reduce ocular inflammation.

Immune responses to adeno-associated virus type 2 encoding channelrhodopsin-2 in a genetically blind rat model for gene therapy

“…These findings are consistent with those of previous reports. 15,27 However, we did not observe such inflammatory cells in the retinas treated with rAAV-Venus or rAAV-ChR2V. Therefore, rAAV-ChR2V administration did not induce inflammation arising from bacterial infection.…”

“…27 After deep anaesthesia, the chest cavity was opened, a 20-gauge perfusion cannula was introduced into the aorta and a part of the liver was excised. After injection of 20 ml PBS to remove erythrocytes and non-adherent leucocytes, 20 ml of fluorescein isothiocyanate-conjugated concanavalin A lectin (40 mg ml À1 ) was injected.…”

(Pro)renin receptor is associated with angiogenic activity in proliferative diabetic retinopathy

“…In this study, we investigated localisation and expression of (P)RR in fibrovascular tissues and vitreous fluids from patients with PDR and evaluated the molecular mechanisms in vitro to confirm ideas about (P)RR from previous animal studies [14,[17][18][19][20][21]. We herein report the first evidence of a close association between (P)RR and angiogenic activity in human PDR.…”

“…Clinical trials have found that angiotensin II type 1 receptor (AT1R) blockade resulted in beneficial effects on the incidence and progression of diabetic retinopathy [7,8]. We have previously revealed, using animal models of diabetes, the molecular mechanisms by which tissue RAS promotes retinal inflammation and angiogenesis [9][10][11][12], while RAS components proved to be present in the retina [11,13,14]. These multiple reports suggest that tissue RAS activation in the retina is a significant risk factor in the development of diabetic retinopathy.…”

“…Prorenin binding to (P)RR activates RAS-independent signal transduction via mitogenactivated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) 1/2 and p38, both of which contribute to the pathogenesis of organ damage [15,16]. The dual activation of tissue RAS and RAS-independent signalling pathways, referred to as the receptor-associated prorenin system (RAPS), has been shown to be involved in the molecular pathogenesis of retinal vascular disorders such as inflammation and angiogenesis [14,[17][18][19][20][21].…”