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Vitreous renin activity correlates with vascular endothelial growth factor in proliferative diabetic retinopathy
  1. Atsuhiro Kanda1,2,
  2. Kousuke Noda1,2,
  3. Wataru Saito2,
  4. Susumu Ishida1,2
  1. 1 Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  2. 2 Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  1. Correspondence to Professor Susumu Ishida Department of Ophthalmology, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan; ishidasu{at}

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The renin-angiotensin system (RAS), a controller of systemic blood pressure (circulatory RAS), plays distinct roles in inflammation and angiogenesis in organs (tissue RAS). Pharmacological blockade of angiotensin II type 1 receptor inhibited the incidence and progression of diabetic retinopathy (DR) in recent clinical trials.1 We unravelled the molecular mechanisms in which tissue RAS causes retinal inflammation2 and the critical roles of (pro)renin receptor ((P)RR) in retinal RAS activation.3 (P)RR binds with prorenin to exert renin activity through the conformational change of the prorenin (for tissue RAS) instead of the proteolysis of the prorenin prosegment (for circulatory RAS). Furthermore, prorenin binding to (P)RR activates RAS-independent signal transduction. The (P)RR-mediated dual activation of tissue RAS and RAS-independent signalling pathways, referred to as the receptor-associated prorenin system (RAPS), was shown to facilitate vascular endothelial growth factor (VEGF)-driven pathogenesis of non-proliferative DR in mice.3

We further reported that the intravitreal levels of soluble form of (P)RR (s(P)RR), released from neovascular endothelial cells in fibrovascular tissues, increased in the patients with proliferative DR (PDR) and correlated with vitreous prorenin and VEGF levels.4 This leads to a novel concept for the molecular pathogenesis of tissue RAS …

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