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Recent Developments in the Regulation of Kinins pp 111–143Cite as

The Kallikrein-Kinin System in Diabetic Retinopathy

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Part of the book series: Progress in Drug Research ((PDR,volume 69))

Abstract

Diabetic retinopathy (DR) is a major microvascular complication associated with type 1 and type 2 diabetes mellitus, which can lead to visual impairment and blindness. Current treatment strategies for DR are mostly limited to laser therapies, steroids, and anti-VEGF agents, which are often associated with unwanted side effects leading to further complications. Recent evidence suggests that kinins play a primary role in the development of DR through enhanced vascular permeability, leukocytes infiltration, and other inflammatory mechanisms. These deleterious effects are mediated by kinin B1 and B2 receptors, which are expressed in diabetic human and rodent retina. Importantly, kinin B1 receptor is virtually absent in sane tissue, yet it is induced and upregulated in diabetic retina. These peptides belong to the kallikrein-kinin system (KKS), which contains two separate and independent pathways of regulated serine proteases, namely plasma kallikrein (PK) and tissue kallikrein (TK) that are involved in the biosynthesis of bradykinin (BK) and kallidin (Lys-BK), respectively. Hence, ocular inhibition of kallikreins or antagonism of kinin receptors offers new therapeutic avenues in the treatment and management of DR. Herein, we present an overview of the principal features and known inflammatory mechanisms associated with DR along with the current therapeutic approaches and put special emphasis on the KKS as a new and promising therapeutic target due to its link with key pathways directly associated with the development of DR.

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Abbreviations

ACE:

Angiotensin-converting enzyme

AGE:

Advanced glycation end products

BRB:

Blood–retinal barrier

BK:

Bradykinin

B1R:

Bradykinin receptor 1

B2R:

Bradykinin receptor 2

C1-INH:

Complement 1 inhibitor

Cox-2:

Cyclooxygenase-2

DME:

Diabetic macular edema

DR:

Diabetic retinopathy

eNOS:

Endothelial nitric oxide synthase

FXII:

Factor XII

HMWK:

High molecular weight kininogen

HIF-1:

Hypoxia inducible factor-1

iNOS:

Inducible nitric oxide synthase

IL-1 β:

Interleukin-1 beta

ICAM-1:

Intercellular adhesion molecule1

IGF:

Insulin-like growth factor

KKS:

Kallikrein-kinin system

LMWK:

Low molecular weight kininogen

NFk-B:

Transcriptional nuclear factor-kappa B

PLA2 :

Phospholipase A2

PK:

Plasma kallikrein

PPK:

Plasma prekallikrein

PKC:

Protein kinase C

ROS:

Reactive oxygen species

NO:

Nitric oxide

NPDR:

Nonproliferative diabetic retinopathy

PDR:

Proliferative diabetic retinopathy

RAS:

Renin–angiotensin system

STZ:

Streptozotocin

O •−2 :

Superoxide anion

TK:

Tissue kallikrein

TNF-α:

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factor

VEGFR-1:

Vascular endothelial growth factor receptor 1

VEGFR-2:

Vascular endothelial growth factor receptor 2

References

  • Abdouh M, Khanjari A, Abdelazziz N, Ongali B, Couture R, Hassessian H (2003) Early upregulation of kinin B1 receptors in retinal microvessels of the streptozotocin-diabetic rat. Br J Pharmacol 140(1):33–40

    CAS  PubMed Central  PubMed  Google Scholar 

  • Abdouh M, Talbot S, Couture R, Hassessian H (2008) Retinal plasma extravasation in streptozotocin-diabetic rats mediated by kinin B(1) and B(2) receptors. Br J Pharmacol 154(1):136–143

    CAS  PubMed Central  PubMed  Google Scholar 

  • Abe Y, Kayakiri H, Satoh S, Inoue T, Sawada Y, Inamura N (1998) A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2. Overcoming the species difference between guinea pig and man. J Med Chem 41(21):4053–4061

    CAS  PubMed  Google Scholar 

  • Abu El-Asrar A, Desmet S, Meersschaert A, Dralands L, Missotten L, Geboes K (2001) Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus. Am J Ophthalmol 132(4):551–556

    CAS  PubMed  Google Scholar 

  • Adamis A, Miller J, Bernal M, D’Amico D, Folkman J, Yeo T, Yeo K (1994) Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 118(4):445–450

    CAS  PubMed  Google Scholar 

  • Aiello L, Avery R, Arrigg P, Keyt B et al (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    CAS  PubMed  Google Scholar 

  • Aiello L, Northrup J, Keyt B, Takagi H, Iwamoto M (1995) Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 113(12):1538–1544

    CAS  PubMed  Google Scholar 

  • Aizu Y, Oyanagi K, Hu J, Nakagawa H (2002) Degeneration of retinal neuronal processes and pigment epithelium in the early stage of streptozotocindiabetic rats. Neropathology 22(3):161–170

    Google Scholar 

  • Akduman L, Olk R (1998) The early treatment for diabetic retinopathy study. In: Kertes C (ed) Clinical trials in ophthalmology: a summary and practice guide. William and Wilkins, Baltimore, pp 15–36

    Google Scholar 

  • Amano S, Yamagishi S, Inagaki Y, Oka- moto T (2003) Angiotensin II stimulates plate- let-derived growth factor-B gene expression in cultured retinal pericytes through intracellular reactive oxygen species generation. Int J Tissue React 25(2):51–55

    Google Scholar 

  • Antonetti D, Barber A, Bronson S, Freeman W, Gardner T, Jefferson L, Kester M, Kimball S, Krady J et al (2006) Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 55(9):2401–2411

    CAS  PubMed  Google Scholar 

  • Antonetti D, Barber A, Khin S, Lieth E, Tarbell J, Gardner T (1998) Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes 47(12):1953–1959

    CAS  PubMed  Google Scholar 

  • Antonetti D, Klein R, Gardner T (2012) Diabetic retinopathy. N Engl J Med 366(13):1227–1239

    Google Scholar 

  • Araujo R, Kettritz R, Fichtner I, Paiva AC, Pesquero J, Bader M (2001) Altered neutrophil homeostasis in kinin B1 receptor-deficient mice. Biol Chem 382(1):91–95

    CAS  PubMed  Google Scholar 

  • Arevalo J, Garcia-Amaris R (2009) Intravitreal bevacizumab for diabetic retinopathy. Curr Diabetes Rev 5(1):39–46

    CAS  PubMed  Google Scholar 

  • Auckland K, Reed R (1993) Interstitial–lymphatic mechanisms in the control of extracellular fluid volume. Physiol Rev 73(1):1–78

    Google Scholar 

  • Ayalasomayajula S, Amrite A, Kompella U (2004) Inhibition of cyclooxygenase-2, but not cyclooxygenase-1, reduces prostaglandin E2 secretion from diabetic rat retinas. Eur J Pharmacol 498(1–3):275–278

    CAS  PubMed  Google Scholar 

  • Ayalasomayajula S, Kompella U (2003) Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular endothelial growth factor expression and vascular leakage in a streptozotocin-induced diabetic rat model. Eur J Pharmacol 458(3):283–289

    CAS  PubMed  Google Scholar 

  • Bader M (2009) Kallikrein Kinin system in Neovascularization. Arterioscler Thromb Vasc Biol 29(5):617–619

    CAS  PubMed  Google Scholar 

  • Bainbridge J, Mistry A, De Alwis M, Paleolog E, Baker A, Thrasher A, Ali R (2002) Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther 9(5):320–326

    CAS  PubMed  Google Scholar 

  • Barber A, Antonetti D, Gardner T (2000) Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. The Penn State Retina Research Group. Invest Ophthalmol Vis Sci 41(11):3561–3568

    CAS  PubMed  Google Scholar 

  • Bates D, Harper S (2002) Regulation of vascular permeability by vascular endothelial growth factors. Vascul Pharmacol 39(4–5):225–237

    CAS  PubMed  Google Scholar 

  • Bearse M, Han Y, Schneck M, Barez S, Jacobsen C, Adams A (2004) Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci 45(9):3259–3265

    PubMed  Google Scholar 

  • Bhavsar A (2006) Diabetic retinopathy: the latest in current management. Retina 26(6):S71–79

    PubMed  Google Scholar 

  • Bhavsar A, Grillone L, McNamara T, Gow J, Hochberg A, Pearson R (2008) Predicting response of vitreous hemorrhage after intravitreous injection of highly purified ovine hyaluronidase (Vitrase) in patients with diabetes. Invest Ophthalmol Vis Sci 49(10):4219–4225

    PubMed  Google Scholar 

  • Bhoola K, Ramsaroop R, Plendl J, Cassim B, Dlamini Z, Naicker S (2001) Kallikrein and kinin receptor expression in inflammation and cancer. Biol Chem 382(1):77–89

    CAS  PubMed  Google Scholar 

  • Bjorkqvist J, Jamsa A, Renne T (2013) Plasma kallikrein: the bradykininproducing enzyme. Thromb Haemost 110(3):399–407

    CAS  PubMed  Google Scholar 

  • Blaes N, Girolami J (2013) Targeting the ‘Janus face’ of the B2-bradykinin receptor. Exp Opin Ther Targets 17(10):1145–1166

    CAS  Google Scholar 

  • Blair N, Feke G, Morales-Stoppello J, Riva C, Goger D, Collas G, McMeel J (1982) Prolongation of the retinal mean circulation time in diabetes. Arch Ophthalmol 100(5):764–768

    CAS  PubMed  Google Scholar 

  • Bockmann S, Paegelow I (2000) Kinins and kinin receptors: importance for the activation of leukocytes. J Leukoc Biol 68(5):587–592

    CAS  PubMed  Google Scholar 

  • Brovkovych V, Zhang Y, Brovkovych S, Minshall R, Skidgel R (2011) A novel pathway for receptor-mediated post-translational activation of inducible nitric oxide synthase. J Cell Mol Med 15(2):258–269

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bucci M, Roviezzo F, Posadas I, Yu J, Parente L, Sessa W, Ignarro L, Cirino G (2005) Endothelial nitric oxide synthase activation is critical for vascular leakage during acute inflammation in vivo. Proc Natl Acad Sci USA 102(3):904–908

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bursell S, Clermont A, Kinsley B, Simonson D, Aiello L, Wolpert H (1996) Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy. Invest Ophthalmol Vis Sci 37(5):886–897

    CAS  PubMed  Google Scholar 

  • Bursell S, Clermont A, Shiba T, King G (1992) Evaluating retinal circulation using video fluorescein angiography in control and diabetic rats. Curr Eye Res 11(4):287–295

    CAS  PubMed  Google Scholar 

  • Campos M, Souza G, Calixto J (1999) In vivo B1 kinin-receptor upregulation. Evidence for involvement of protein kinases and nuclear factor κB pathways. Br J Pharmacol 127(8):1851–1859

    Google Scholar 

  • Catanzaro O, Dziubecki D, Obregon P, Rodriguez R, Sirois P (2010) Antidiabetic efficacy of bradykinin antagonist R-954 on glucose tolerance test in diabetic type 1 mice. Neuropeptides 44(2):187–189

    CAS  PubMed  Google Scholar 

  • Catanzaro O, Labal E, Andornino A, Capponi J, Di Marttino I, Sirois P (2012) Blockade of early and late retinal biochemical alterations associated with diabetes development by the selective bradykinin B1 receptor antagonist R954. Peptides 34(2):349–352

    CAS  PubMed  Google Scholar 

  • Ceravolo G, Fernandes F, Munhoz C, Fernandes D, Tostes R, Laurindo F, Scavone C, Fortes Z, Carvalho M (2007) Angiotensin II chronic infusion induces B1 receptor expression in aorta of rats. Hypertension 50(4):756–761

    CAS  PubMed  Google Scholar 

  • Chakrabarti S, Cukiernik M, Hileeto D, Evans T, Chen S (2000) Role of vasoactive factors in the pathogenesis of early changes in diabetic retinopathy. Diabetes Metab Res Rev 16(6):393–407

    CAS  PubMed  Google Scholar 

  • Chase H, Garg S, Harris S, Hoops S, Jackson W, Holmes D (1993) Angiotensinconverting enzyme inhibitor treatment for young normotensive diabetic subjects; a two year trial. Ann Ophthalmol 25(8):284–289

    CAS  PubMed  Google Scholar 

  • Chaturvedi N, Porta M, Klein R, Orchard T, Fuller J, Parving H, Bilous R, Sjolie A, Group. DPS (2008) Effect of candesartan on prevention (DIRECTPrevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 372(9647):1394–1402

    Google Scholar 

  • Chaturvedi N, Sjolie A, Stephenson J, Abrahamian H, Keipes M, Castellarin A, Rogulja-Pepeonik Z, Fuller J (1998) Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB controlled trial of lisinopril in insulin dependent diabetes mellitus. Lancet 351(9095):28–31

    CAS  PubMed  Google Scholar 

  • Cheung N, Mitchell P, Wong T (2010) Diabetic retinopathy. Lancet 376(9735):124–136

    PubMed  Google Scholar 

  • Chihara E, Matsuoka T, Ogura Y, Matsumura M (1993) Retinal nerve fiber layer defect as an early manifestation of diabetic retinopathy. Ophthalmology 100(8):1147–1151

    CAS  PubMed  Google Scholar 

  • Chung H, Lee H, Lamoke F, Hrushesky H, Wood P, Jahng W (2009) Neuroprotective role of erythropoietin by anti-apoptosis in the retina. J Neurosci Res 87(10):2365–2374

    CAS  PubMed  Google Scholar 

  • Clermont A, Aiello L, Mori F, Aiello L, Bursell S (1997) Vascular endothelial growth factor and severity of nonproliferative diabetic retinopathy mediate retinal hemodynamics in vivo: a potential role for vascular endothelial growth factor in the progression of nonproliferative diabetic retinopathy. Am J Ophthalmol 124(4):433–446

    CAS  PubMed  Google Scholar 

  • Clermont A, Brittis M, Shiba T, McGovern T, King G, Bursell S (1994) Normalization of retinal blood flow in diabetic rats with primary intervention using insulin pumps. Invest Ophthalmol Vis Sci 35(3):981990

    Google Scholar 

  • Clermont A, Bursell S, Feener E (2006) Role of the angiotensin II type 1 receptor in the pathogenesis of diabetic retinopathy: effects of blood pressure control and beyond. J Hypertens Suppl 24(1):S73–80

    CAS  PubMed  Google Scholar 

  • Clermont A, Chilcote T, Kita T, Liu J, Riva P, Sinha S, Feener E (2011) Plasma kallikrein mediates retinal vascular dysfunction and induces retinal thickening in diabetic rats. Diabetes 60(5):1590–1598

    CAS  PubMed Central  PubMed  Google Scholar 

  • Colman R, Pixley R, Sainz I, Song J, Isordia-Salas I, Muhamed S, Powell J, Mousa S (2003) Inhibition of angiogenesis by antibody blocking the action of proangiogenic high-molecular-weight kininogen. J Thromb Haemost 1(1):164–170

    CAS  PubMed  Google Scholar 

  • Couture R, Girolami J (2004) Putative roles of kinin receptors in the therapeutic effects of angiotensin 1-converting enzyme inhibitors in diabetes mellitus. Eur J Pharmacol 500(1–3):467–485

    CAS  PubMed  Google Scholar 

  • Couture R, Harrisson M, Vianna R, Cloutier F (2001) Kinin receptors in pain and inflammation. Eur J Pharmacol 429(1–3):161–176

    CAS  PubMed  Google Scholar 

  • Crane I, Liversidge J (2008) Mechanisms of leukocyte migration across the blood–retina barrier. Semin Immunopathol 30(2):165–177

    PubMed Central  PubMed  Google Scholar 

  • Cunha-Vaz J, Fonscera J, Abreu J (1978a) Vitreous fluorophotometry and retinal blood flow studies in proliferative retinopathy. Graefes Arch Clin Exp Ophthalmol 207(2):71–76

    CAS  Google Scholar 

  • Cunha-Vaz J, Fonscera J, de Abreu J, Lima J (1978b) Studies on retinal blood flow. Arch Ophthalmol 96(5):809–811

    CAS  PubMed  Google Scholar 

  • Cyr M, Lepage Y, Blais C, Gervais N, Cugno M, Rouleau J, Adam A (2001) Bradykinin and des-Arg(9)-bradykinin metabolic pathways and kinetics of activation of human plasma. Am J Physiol Heart Circ Physiol 281(1):H275–H283

    CAS  PubMed  Google Scholar 

  • De Brito Gariepy H, Talbot S, Senecal J, Couture R (2013) Brain kinin B1 receptor contributes to the onset of stereotypic nocifensive behavior in rat. Behav Brain Res 241:17–26

    Google Scholar 

  • Del Mashio A, Zanetti A, Corada M, Rival Y, Ruco L, Lampugnani M, Dejana E (1996) Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions. J Cell Biol 135(2):749–751

    Google Scholar 

  • Dias J, Talbot S, Senecal J, Carayon P, Couture R (2010) Kinin B1 receptor enhances the oxidative stress in a rat model of insulin resistance: outcome in hypertension, allodynia and metabolic complications. PLoS ONE 5(9):e12622

    PubMed Central  PubMed  Google Scholar 

  • Du Y, Sarthy V, Kern T (2004) Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats. Am J Physiol Regul Integr Comp Physiol 287(4):R735–741

    CAS  PubMed  Google Scholar 

  • Duchene J, Lecomte F, Ahmed S, Cayla C, Pesquero J, Bader M, Perretti M, Ahluwalia A (2007) A novel inflammatory pathway involved in leukocyte recruitment: role for the kinin B1 receptor and the chemokine CXCL5. J Immunol 179(7):4849–4856

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ebrahimian T, Tamarat R, Clergue M, Duriez M, Levy B, Silvestre J (2005) Dual effect of angiotensin-converting enzyme inhibition on angiogenesis in type 1 diabetic mice. Arterioscler Thromb Vasc Biol 25(1):65–70

    CAS  PubMed  Google Scholar 

  • El-Asrar A (2012) Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East Afr J Ophthalmol 19(1):70–74

    PubMed Central  PubMed  Google Scholar 

  • Famiglietti E, Stopa E, McGookin E, Song P, LeBlanc V, Streeten B (2003) Immunocytochemical localization of vascular endothelial growth factor in neurons and glial cells of human retina. Brain Res 969(1–2):195–204

    CAS  PubMed  Google Scholar 

  • Feke G, Tagawa H, Yoshida A, Goger D, Weiter J, Buzney S, McMeel J (1985) Retinal circulatory changes related to retinopathy progression in insulin- dependent diabetes mellitus. Ophthalmology 92(11):1517–1522

    CAS  PubMed  Google Scholar 

  • Fernandes S, Mendonça L, Mandarim-de-Lacerda C (2006) Beneficial effects of angiotensin II AT1 blocker on cardiovascular adverse remodeling due to nitric oxide synthesis blockade. Int J Morphol 24(3):309–318

    Google Scholar 

  • Ferreira AP, Rodrigues FS, Della-Pace ID, Mota BC, Oliveira SM, de Campos Velho Gewehr C, Bobinski F, de Oliveira CV, Brum JS, Oliveira MS, Furian AF, de Barros CS, Dos Santos AR, Ferreira J, Fighera MR, Royes LF et al (2014) HOE-140, an antagonist of B2 receptor, protects against memory deficits and brain damage induced by moderate lateral fluid percussion injury in mice. Psychopharmacol 231(9):1935–1948

    Google Scholar 

  • Fong D, Aiello L, Gardner T, King G, Blankenship G, Cavallerano J et al (2004) Retinopathy in diabetes. Diabetes Care 27(1):S84–S87

    Google Scholar 

  • Fontaine O, Olivier S, Descovich D, Cordahi G, Vaucher E, Lesk M (2011) The effect of intravitreal injection of bevacizumab on retinal circulation in patients with neovascular macular degeneration. Invest Ophthalmol Vis Sci 52(10):7400–7405

    CAS  PubMed  Google Scholar 

  • Frank R (2004) Diabetic retinopathy. N Engl J Med 350(1):48–58

    CAS  PubMed  Google Scholar 

  • Funatsu H, Yamashita H, Nakanishi Y, Hori S (2002) Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy. Br J Ophthalmol 86(3):311–315

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gao B, Clermont A, Rook S, Fonda S, Srinivasan V, Wojtkowski M, Fujimoto J, Avery R, Arrigg P, Bursell S, Aiello L, Feener E (2007) Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat Med 13(2):181188

    Google Scholar 

  • Gao G, Shao C, Zhang S, Dudley A, Fant J, Ma J (2003) Kallikrein-binding protein inhibits retinal neovascularization and decreases vascular leakage. Diabetologia 46(5):689–698

    CAS  PubMed  Google Scholar 

  • Garcia-Ramirez M, Hernandez C, Simo R (2008) Expression of erythropoietin and its receptor in the human retina: a comparative study of diabetic and nondiabetic subjects. Diab Care 31(6):1189–1194

    Google Scholar 

  • Gobeil F, Sirois P, Regoli D (2013) Preclinical pharmacology, metabolic stability, pharmacokinetics and toxicology of the peptidic kinin B1 receptor antagonist R-954. Peptides 52C:82–89

    Google Scholar 

  • Gougat J, Ferrari B, Sarran L, Planchenault C, Poncelet M, Maruani J, Alonso R, Cudennec A et al (2004) SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-Nmethylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization. J Pharmacol Exp Ther 309(2):661–669

    CAS  PubMed  Google Scholar 

  • Grunwald J, Riva C, Baine J, Brucker A (1992) Total retinal volumetric blood flow rate in diabetic patients with poor glycemic control. Invest Ophthalmol Vis Sci 33(2):356–363

    CAS  PubMed  Google Scholar 

  • Grunwald J, Riva C, Sinclair S, Brucker A, Petrig B (1986) Laser Doppler velocimetry study of retinal circulation in diabetes mellitus. Arch Ophthalmol 104(7):991–996

    CAS  PubMed  Google Scholar 

  • Han E, MacFarlane R, Mulligan A, Scafidi J, Davis A (2002) Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor. J Clin Investigation 109(8):1057–1063

    CAS  Google Scholar 

  • Harris M, Ju H, Venema V, Liang H, Zou R, Michell B, Chen Z, Kemp B, Venema R (2001) Reciprocal phosphorylation and regulation of endothelial nitricoxide synthase in response to bradykinin stimulation. J Biol Chem 276(19):16587–16591

    CAS  PubMed  Google Scholar 

  • Hatcher H, Ma J, Chao J, Chao L, Ottlecz A (1997) Kallikrein-binding protein levels are reduced in the retinas of streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 38(3):658–664

    CAS  PubMed  Google Scholar 

  • Hawkins B, Davis T (2005) The Blood-Brain Barrier/Neurovascular Unit in Health and Disease. Pharmacol Rev 57(2):173–185

    CAS  PubMed  Google Scholar 

  • Hetu S (2011) Pharmacologie des variations de debit sanguin ocularies chez le rat au moyen de la debitmetrie au laser par effect doppler. Electronic MSc Thesis http://hdl.handle.net/1866/5295

  • Higashi S, Clermont A, Dhir V, Bursell S (1998) Reversibility of retinal flow abnormalities is disease-duration dependent in diabetic rats. Diabetes 47(4):653–659

    CAS  PubMed  Google Scholar 

  • Hoang Q, Mendonca L, Della T, Jung J, Tsuang A, Freund K (2012) Effect on intraocular pressure in patients receiving unilateral intravitreal anti-vascular endothelial growth factor injections. Ophthalmology 119(2):321–326

    PubMed  Google Scholar 

  • Ikeda Y, Hayashi I, Kamoshita E, Yamazaki A, Endo H, Ishihara K, Yamashina S, Tsutsumi Y, Matsubara H, Majima M (2004) Host stromal bradykinin B2 receptor signaling facilitates tumor-associated angiogenesis and tumor growth. Cancer Res 64(15):5178–5185

    CAS  PubMed  Google Scholar 

  • Ikeda Y, Yonemitsu Y, Onimaru M, Nakano T, Miyazaki M, Kohno R, Nakagawa K, Ueno A, Sueishi K, Ishibashi T (2006) The regulation of vascular endothelial growth factors (VEGF-A, -C, and -D) expression in the retinal pigment epithelium. Exp Eye Res 83(5):1031–1040

    CAS  PubMed  Google Scholar 

  • Inokuchi N, Ikeda T, Imamura Y, Sotozono C, Kinoshita S, Uchihori Y, Nakamura K (2001) Vitreous levels of insulin-like growth factor-I in patients with proliferative diabetic retinopathy. Curr Eye Res 23(5):368–371

    CAS  PubMed  Google Scholar 

  • Ismael M, Talbot S, Carbonneau C, Beausejour C, Couture R (2008) Blockade of sensory abnormalities and kinin B(1) receptor expression by N-acetyl-Lcysteine and ramipril in a rat model of insulin resistance. Eur J Pharmacol 589(1–3):66–72

    CAS  PubMed  Google Scholar 

  • Johnson E, Dunlop M, Larkins R (1999) Increased vasodilatory prostaglandin production in the diabetic rat retinal vasculature. Curr Eye Res 18(2):7982

    Google Scholar 

  • Joseph K, Kaplan A (2005) Formation of bradykinin: a major contributor to the innate inflammatory response. Adv Immunol 86:159

    CAS  PubMed  Google Scholar 

  • Joussen A, Joeres S (2007) Benefits and limitations in vitreoretinal surgery for proliferative diabetic retinopathy and macular edema. Diabet Retinopathy Dev Ophthalmol Basel Karger 39:69–87

    Google Scholar 

  • Joussen A, Murata T, Tsujikawa A, Kirchhof B, Bursell S, Adamis A (2001) Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol 158(1):147–152

    CAS  PubMed Central  PubMed  Google Scholar 

  • Joussen A, Poulaki V, Mitsiades N, Kirchhof B, Koizumi K, Döhmen S, Adamis A (2002a) Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J 16(3):438–440

    CAS  PubMed  Google Scholar 

  • Joussen A, Poulaki V, Tsujikawa A, Qin W, Qaum T, Xu Q, Moromizato Y, Bursell S, Wiegand S, Rudge J, Ioffe E, Yancopoulos G, Adamis A (2002b) Suppression of diabetic retinopathy with angiopoietin-1. Am J Pathol 160(5):1683–1693

    CAS  PubMed Central  PubMed  Google Scholar 

  • Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP (2004) A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 18(12):1450–1452

    CAS  PubMed  Google Scholar 

  • Kedzierska K, Ciechanowski K, Gołembiewska E, Safranow K, Ciechanowicz A, Domański L, Myślak M, Róźański J (2005) Plasma prekallikrein as a risk factor for diabetic retinopathy. Arch Med Res 36(5):539–543

    Google Scholar 

  • Keech A, Mitchell P, Summanen P, O’Day J, Davis T, Moffitt M, Taskinen M, Simes R, Tse D, Williamson E, Merrifield A et al (2007) Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 370(9600):1687–1697

    CAS  PubMed  Google Scholar 

  • Kern T (2007) Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diab Res 95103:1–14

    Google Scholar 

  • Kern T, Miller C, Du Y, Zheng L, Mohr S, Ball S, Kim M, Jamison J, Bingaman D (2007) Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology. Diabetes 56(2):373–379

    CAS  PubMed  Google Scholar 

  • Kim J, Kim J, Yu Y, Cho C, Kim K (2009) Blockade of angiotensin II attenuates VEGF-mediated blood-retinal barrier breakdown in diabetic retinopathy. J Cereb Blood Flow Metab 29(3):621–628

    CAS  PubMed  Google Scholar 

  • Kintsurashvili E, Duka I, Gavras I, Johns C, Farmakiotis D, Gavras H (2001) Effects of ANG II on bradykinin receptor gene expression in cardiomyocytes and vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 281(4):H1778–H1783

    CAS  PubMed  Google Scholar 

  • Klein R, Moss S (1995) Comparison of the study populations in the diabetes control and complications trial and the Wisconsin epidemiologic study of diabetic retinopathy. Arch Intern Med 155(7):745–754

    CAS  PubMed  Google Scholar 

  • Kohner E, Hamilton A, Saunders S, Sutcliffe B, Bulpitt C (1975) The retinal blood flow in diabetes. Diabetologia 11(1):27–33

    CAS  PubMed  Google Scholar 

  • Kowluru G, Bir S, Kevil C (2012) Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med 918267:1–30

    Google Scholar 

  • Kowluru R, Chan P (2007) Oxidative stress and diabetic retinopathy. Exp Diab Res 43603:1–12

    Google Scholar 

  • Kowluru R, Odenbach S (2004) Role of Interleukin-1 in the development of retinopathy in rats: effect of antioxidants. Invest Ophthalmol Vis Sci 45(11):4161–4166

    PubMed  Google Scholar 

  • Krady J, Basu A, Allen C, Xu Y, LaNoue K, Gardner T, Levison S (2005) Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes 54(5):1559–1565

    CAS  PubMed  Google Scholar 

  • Kurihara T, Ozawa Y, Nagai N, Shinoda K, Noda K, Imamura Y, Tsubota K, Okano H, Oike Y, Ishida S (2008) Angiotensin II type 1 receptor signaling contributes to synaptophys in degradation and neuronal dysfunction in the diabetic retina. Diabetes 57(8):2191–2198

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuroki M, Voest E, Amano S, Beerepoot L, Kashima S, Tolentino M, Kim R, Rohan R, Colby K, Yeo K, Adamis A (1996) Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo. J Clin Invest 98(7):1667–1675

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuznetsova T, Chesnokova N, Paskhina T (1991) Activity of tissue and plasma kallikrein and level of their precursors in eye tissue structures and media of healthy rabbits. Vopr Med Khim 37(4):79–82

    CAS  PubMed  Google Scholar 

  • Lacoste B, Tong X, Lahjouji K, Couture R, Hamel E (2013) Cognitive and cerebrovascular improvements following kinin B1 receptor blockade in Alzheimer’s disease mice. J Neuroinflammation 10:57

    CAS  PubMed Central  PubMed  Google Scholar 

  • Larrivee J, Bachvarov D, Houle F, Landry J, Huot J, Marceau F (1998) Role of the mitogen-activated protein kinases in the expression of the kinin B1 receptors induced by tissue injury. J Immunol 160(3):14191426

    Google Scholar 

  • Larsen M, Hommel E, Parving H, Lund-Andersen H (1990) Protective effect of captopril on the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. Graefes Arch Clin Exp Ophthalmol 228(6):505–509

    CAS  PubMed  Google Scholar 

  • Lawson S, Gabra B, Guerin B, Neugebauer W, Nantel F, Battistini B, Sirois P (2005) Enhanced dermal and retinal vascular permeability in streptozotocin-induced type 1 diabetes in Wistar rats: blockade with a selective bradykinin B receptor antagonist. Regul Pept 124(13):221–224

    CAS  PubMed  Google Scholar 

  • Leal E, Manivannan A, Hosoya K, Terasaki T, Cunha-Vaz J, Ambrosio A, Forrester J (2007) Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy. Invest Ophthalmol Vis Sci 48(11):52575265

    Google Scholar 

  • Leeb-Lundberg L, Marceau F, Muller-Esterl W, Pettibone D, Zuraw B (2005) International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 57(1):27–77

    CAS  PubMed  Google Scholar 

  • Li P, Kondo T, Numaguchi Y, Kobayashi K, Aoki M, Inoue N, Okumura K, Murohara T (2008) Role of bradykinin, nitric oxide, and angiotensin II type 2 receptor in imidapril-induced angiogenesis. Hypertension 51(2):252–258

    CAS  PubMed  Google Scholar 

  • Lieth E, Gardner T, Barber A, Antonetti D (2000) Retinal neurodegeneration: early pathology in diabetes. Clin Exp Ophthalmol 28(1):3–8

    CAS  Google Scholar 

  • Liew G, Mitchell P, Wong T (2009) Systemic management of diabetic retinopathy. BMJ 338:b441

    Google Scholar 

  • Liu J, Feener E (2013) Plasma kallikrein-kinin system and diabetic retinopathy. Biol Chem 394(3):319–328

    CAS  PubMed  Google Scholar 

  • Lock J, Fong K (2011) An update on retinal laser therapy. Clin Exp Optom 94(1):43–51

    PubMed  Google Scholar 

  • Lund L, Green K, Stoop A, Ploug M, Almholt K, Lilla J, Nielsen B, Christensen I, Craik C, Werb Z, Danø K, Rømer J (2006) Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice. EMBO J 25(12):2686–2697

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lungu C, Dias J, Franca C, Ongali B, Regoli D, Moldovan F, Couture R (2007) Involvement of kinin B1 receptor and oxidative stress in sensory abnormalities and arterial hypertension in an experimental rat model of insulin resistance. Neuropeptides 41(6):375–387

    CAS  PubMed  Google Scholar 

  • Ma J, Song Q, Hatcher H, Crouch R, Chao L, Chao J (1996) Expression and cellular localization of the kallikrein-kinin system in human ocular tissues. Exp Eye Res 63(1):19–26

    CAS  PubMed  Google Scholar 

  • Maas C, Govers-Riemslag J, Bouma B, Schiks B, Hazenberg B, Lokhorst H, Hammarström P, ten Cate H, de Groot P, Bouma B, Gebbink M (2008) Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation. J Clin Invest 118(9):3208–3218

    CAS  PubMed Central  PubMed  Google Scholar 

  • Madeddu P, Emanueli C, El Dahr S (2007) Mechanisms of disease: the tissue kallikrein-kinin system in hypertension and vascular remodeling. Nat Clin Pract Nephrol 3(4):208–221

    CAS  PubMed  Google Scholar 

  • Madsen-Bouterse S, Kowluru R (2008) Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Rev Endocr Metab Disord 9(4):315–327

    CAS  PubMed  Google Scholar 

  • Mara L, Oates PJ (2008) The polyol pathway and diabetic retinopathy. Contemp Diab Diabet Retinopathy 159–186. doi: 10.1007/978-1-59745-563-3_6

    Google Scholar 

  • Marceau F (1995) Kinin B1 receptors: a review. Immunopharmacology 30(1):126

    Google Scholar 

  • Marceau F, Hess J, Bachvarov D (1998) The B1 receptors for kinins. Pharmacol Rev 50(3):357–386

    CAS  PubMed  Google Scholar 

  • Mason G, Cumberbatch M, Hill R, Rupniak N (2002) The bradykinin B1 receptor antagonist B9858 inhibits a nociceptive spinal reflex in rabbits. Can J Physiol Pharmacol 80(4):264–268

    CAS  PubMed  Google Scholar 

  • Matsubara H (1998) Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ Res 83(12):1182–1191

    CAS  PubMed  Google Scholar 

  • McLean P, Ahluwalia A, Perretti M (2000) Association between kinin B(1) receptor expression and leukocyte trafficking across mouse mesenteric postcapillary venules. J Exp Med 192(3):367–380

    CAS  PubMed Central  PubMed  Google Scholar 

  • McLeod D, Lefer D, Merges C, Lutty G (1995) Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid. Am J Pathol 147(3):642–653

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meini S, Cucchi P, Catalani C, Bellucci F, Santicioli P, Giuliani S, Maggi C (2010) Radioligand binding characterization of the bradykinin B(2) receptor in the rabbit and pig ileal smooth muscle. Eur J Pharmacol 635(1):34–39

    CAS  PubMed  Google Scholar 

  • Michaelides M, Fraser-Bell S, Hamilton R, Kaines A, Egan C, Bunce C, Peto T, Hykin P (2010) Macular perfusion determined by fundus fluorescein angiography at the 4-month time point in a prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (bolt study): report1. Retina 30(5):781–786

    PubMed  Google Scholar 

  • Milne R, Brownstein S (2011) Advanced glycation endproducts and diabetic retinopathy. Amino Acids 44(6):1397–1407

    PubMed  Google Scholar 

  • Miyamoto K, Hiroshiba N, Tsujikawa A, Ogura Y (1998) In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci 39(11):2190–2194

    CAS  PubMed  Google Scholar 

  • Miyamoto K, Khosrof S, Bursell S, Rohan R, Murata T, Clermont A, Aiello L, Ogura Y, Adamis A (1999) Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci USA 96(19):10836–10841

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miyamoto K, Ogura Y, Nishiwaki H, Matsuda N, Honda Y, Kato S, Ishida H, Seino Y (1996) Evaluation of retinal microcirculatory alterations in the Goto-Kakizaki rat. A spontaneous model of non-insulin-dependent diabetes. Invest Ophthalmol Vis Sci 37(5):898–905

    CAS  PubMed  Google Scholar 

  • Mohamed Q, Gillies M, Wong T (2007) Management of diabetic retinopathy: a systematic review. JAMA 298(8):902–916

    CAS  PubMed  Google Scholar 

  • Morand-Contant M, Anand-Srivastava M, Couture R (2010) Kinin B1 receptor upregulation by angiotensin II and endothelin-1 in rat vascular smooth muscle cells: receptors and mechanisms. Am J Physiology Heart Circ Physiol 299(5):H1625–H1632

    CAS  Google Scholar 

  • Moreau M, Garbacki N, Molinaro G, Brown N, Marceau F, Adam A (2005) The kallikrein kinin system: current and future pharmacological targets. J Pharmacol 99(1):6–38

    CAS  Google Scholar 

  • Muller F, Mutch N, Schenk W, Smith S, Esterl L, Spronk H, Schmidbauer S, Gahl W, Morrissey J, Renné T (2009) Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 139(6):1143–1156

    CAS  PubMed Central  PubMed  Google Scholar 

  • Naveh-Floman N, Weissman C, Belkin M (1984) Arachidonic acid metabolism by retinas of rats with streptozotocin-induced diabetes. Curr Eye Res 3(9):1135–1139

    CAS  PubMed  Google Scholar 

  • Network DRCR (2008) A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 115(9):1447–1449

    Google Scholar 

  • Ni A, Chao L, Chao J (1998) Transcription factor nuclear factor kappaB regulates the inducible expression of the human B1 receptor gene in inflammation. J Biol Chem 273(5):2784–2791

    CAS  PubMed  Google Scholar 

  • Ni A, Yin H, Agata J, Yang Z, Chao L, Chao J (2003) Overexpression of kinin B1 receptors induces hypertensive response to des-Arg9-bradykinin and susceptibility to inflammation. J Biol Chem 278(1):219–225

    CAS  PubMed  Google Scholar 

  • Orsenigo C, Giampietro C, Ferrari A, Corada M et al (2012) Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo. Nat Commun 3:1208

    PubMed Central  PubMed  Google Scholar 

  • Oschatz C, Maas C, Lecher B et al (2011) Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity 34(2):258–268

    Google Scholar 

  • Parenti A, Morbidelli L, Ledda F, Granger H, Ziche M (2001) The bradykinin/B1 receptor promotes angiogenesis by up-regulation of endogenous FGF-2 in endothelium via the nitric oxide synthase pathway. FASEB J 15(8):14871489

    Google Scholar 

  • Park S, Park J, Park S, Kim K, Chung J, Chun M, Oh S (2003) Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina. Diabetologia 46(9):1260–1268

    Google Scholar 

  • Patel V, Rassam S, Newsom R, Wiek J, Kohner E (1992) Retinal blood flow in diabetic retinopathy. BMJ 305(6855):678–683

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pesquero J, Araujo R, Heppenstall P, Stucky C, Silva J Jr, Walther T, Oliveira S, Pesquero J, Paiva A, Calixto J, Lewin G, Bader M (2000) Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors. Proc Natl Acad Sci USA 97(14):8140–8145

    CAS  PubMed Central  PubMed  Google Scholar 

  • Phipps J, Clermont A, Sinha S, Chilcote T, Bursell S, Feener E (2008) Plasma kallikrein mediates angiotensin II type 1 receptor-stimulated retinal vascular permeability. Hypertension 53(2):175–181

    Google Scholar 

  • Phipps J, Feener E (2008) The kallikrein-kinin system in diabetic retinopathy: lessons for the kidney. Kidney Int 73(10):1114–1119

    CAS  PubMed  Google Scholar 

  • Pietrovski E, Paludo K, Mendes D, Guimarães F, Veiga S, Buchi D, Fonseca R et al (2011) B1 and B2 kinin receptor participation in hyperproliferative and inflammatory skin processes in mice. J Dermatol Sci 64(1):23–30

    CAS  PubMed  Google Scholar 

  • Pinna A, Emanueli C, Dore S, Salvo M, Madeddu P, Carta F (2004) Levels of human tissue kallikrein in the vitreous fluid of patients with severe proliferative diabetic retinopathy. Ophthalmologica 218(4):260–263

    CAS  PubMed  Google Scholar 

  • Porreca F, Vanderah T, Guo W, Barth M, Dodey P, Peyrou V, Luccarini J, Junien J, Pruneau D (2006) Antinociceptive pharmacology of N-[[4-(4,5-dihydro1H-imidazol-2-yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl) sulfonyl]methylamino]ethoxy]-N-methylacetamide, fumarate (LF22-0542), a novel nonpeptidic bradykinin B1 receptor antagonist. J Pharmacol Exp Ther 18(1):195–205

    Google Scholar 

  • Pouliot M, Hetu S, Lahjouji K, Couture R, Vaucher E (2011) Modulation of retinal blood flow by kinin B receptor in Streptozotocin-diabetic rats. Exp Eye Res 92(6):482–489

    CAS  PubMed  Google Scholar 

  • Pouliot M, Talbot S, Sénécal J, Dotigny F, Vaucher E, Couture R (2012) Ocular application of the kinin B1 receptor antagonist LF22-0542 inhibits retinal inflammation and oxidative stress in streptozotocin-diabetic rats. PloS ONE 7(3):e33864

    Google Scholar 

  • Prado G, Taylor L, Zhou X, Ricupero D, Mierke D, Polgar P (2002) Mechanisms regulating the expression, self-maintenance, and signaling-function of the bradykinin B2 and B1 receptors. J Cell Physiol 193(3):275–286

    CAS  PubMed  Google Scholar 

  • Pruneau D, Paquet J, Luccarini J, Defrêne E, Fouchet C, Franck R, Loillier B, Robert C, Bélichard P, Duclos H, Cremers B, Dodey P (1999) Pharmacological profile of LF 16-0687, a new potent non-peptide bradykinin B2 receptor antagonist. Immunopharmacology 43(2–3):187194

    Google Scholar 

  • Pugliese G, Tilton RG, Speedy A, Santarelli E, Eades D, Province M, Kilo C, Sherman W, Williamson J (1990) Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol. Diabetes 39(3):312–322

    CAS  PubMed  Google Scholar 

  • Qaum T, Xu Q, Joussen A, Clemens M, Qin W, Miyamoto K, Hassessian H, Wiegand S, Rudge J, Yancopoulos G, Adamis A (2001) VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest Ophthalmol Vis Sci 42(10):2408–2413

    CAS  PubMed  Google Scholar 

  • Regoli D, Barabe J (1980) Pharmacology of bradykinin and related kinins. Pharmacol Rev 32(1):1–46

    CAS  PubMed  Google Scholar 

  • Regoli D, Nsa Allogho S, Rizzi A, Gobeil F (1998) Bradykinin receptors and their antagonists. Eur J Pharmacol 348(1):1–10

    Google Scholar 

  • Regoli D, Plante G, Gobeil F (2012) Impact of kinins in the treatment of cardiovascular diseases. Pharmacol Ther 135(1):94–111

    CAS  PubMed  Google Scholar 

  • Regoli D, Rhaleb N, Drapeau G, Dion S, Tousignant C, D’Orléans-Juste P, Devillier P (1989) Basic pharmacology of kinins: pharmacologic receptors and other mechanisms. Adv Exp Med Biol 247A:399–407

    CAS  PubMed  Google Scholar 

  • Rodriguez-Fontal M, Kerrison J, Alfaro D, Jablon E (2009) Metabolic control and diabetic retinopathy. Curr Diabetes Rev 5(1):3–7

    CAS  PubMed  Google Scholar 

  • Romero-Aroca P, Baget-Bernaldiz M, Fernandez-Ballart J, Plana-Gil N, SolerLluis N, Mendez-Marin I, Bautista-Perez A (2011) Ten-year incidence of diabetic retinopathy and macular edema. Risk factors in a sample of people with type 1 diabetes. Diab Res Clin Pract 94(1):126–132

    Google Scholar 

  • Rosen E, Spiegelman B (2001) PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 276(41):37731–37734

    CAS  PubMed  Google Scholar 

  • Ruberte J, Ayuso E, Navarro M, Carretero A, Nacher V, Haurigot V, George M, Llombart C, Casellas A, Costa C, Bosch A, Bosch F (2013) Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease. J Clin Investig 113(8):1149–1157

    Google Scholar 

  • Sawutz D, Salvino J, Dolleo R, Casiano F, Ward S, Houck W, Faunce D et al (1994) The nonpeptide WIN 64338 is a bradykinin B2 receptor antagonist. Proc Natl Acad Sci USA 91:4693–4697

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schmaier A, McCrae K (2007) The plasma kallikrein-kinin system: its evolution from contact activation. J Thromb Haemost 5(12):2323–2329

    CAS  PubMed  Google Scholar 

  • Selvarajan S, Lund L, Takeuchi T, Craik C, Werb Z (2001) A plasma kallikreindependent plasminogen cascade required for adipocyte differentiation. Nat Cell Biol 3(3):267–275

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shaposhnikov M, Latkin D, Plyusnina E, Shilova L, Danilov A, Popov S, Zhavoronkov A, Ovodov Y, Moskalev A (2013) The effects of pectins on life span and stress resistance in Drosophila melanogaster. Biogerontology 15(2):113–127

    Google Scholar 

  • Shigematsu S, Ishida S, Gute D, Korthuis R (2002) Bradykinin-induced proinflammatory signaling mechanisms. Am J Physiol Heart Circ Physiol 283(6):H2676–H2686

    CAS  PubMed  Google Scholar 

  • Sigurdsson S, Paulson O, Hoj N, Strandgaard S (2013) Bradykinin antagonist counteracts the acute effect of both angiotensin-converting enzyme inhibition and of angiotensin receptor blockade on the lower limit of autoregulation of cerebral blood flow. J Cereb Blood Flow Metab 34(3):467–471

    Google Scholar 

  • Silva K, Rosales M, Biswas S, Lopes de Faria J, Lopes de Faria J (2009) Diabetic retinal neurodegeneration is associated with mitochondrial oxidative stress and is improved by an angiotensin receptor blocker in a model combining hypertension and diabetes. Diabetes 58(6):1382–1390

    Google Scholar 

  • Simard B, Gabra B, Sirois P (2002) Inhibitory effect of a novel bradykinin B1 receptor antagonist, R-954, on enhanced vascular permeability in type 1 diabetic mice. Can J Physiol Pharmacol 80(12):1203–1207

    CAS  PubMed  Google Scholar 

  • Simmon V (2009) Response to: The BRAIN TRIAL: a randomised, placebo controlled trial of a bradykinin B2 receptor antagonist (anatibant) in patients with traumatic brain injury. Trials 10:110

    PubMed Central  PubMed  Google Scholar 

  • Simo R, Carrasco E, Garcia-Ramirez M, Hernandez C (2006) Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabet Rev 2(1):71–98

    CAS  Google Scholar 

  • Simo R, Hernandez C (2009) Advances in the Medical Treatment of Diabetic Retinopathy. Diab Care 32(8):1556–1562

    CAS  Google Scholar 

  • Sone H, Kawakami Y, Okuda Y, Sekine Y, Honmura S, Matsuo K, Segawa T, Suzuki H, Yamashita K (1997) Ocular vascular endothelial growth factor levels in diabetic rats are elevated before observable retinal proliferative changes. Diabetologia 40(6):726–730

    CAS  PubMed  Google Scholar 

  • Stewart J (2004) Bradykinin antagonists: discovery and development. Peptides 25(3):527–532

    Google Scholar 

  • Stewart J, Gera L, Chan D, Whalley E, Hanson W, Zuzack J (1997) Potent, longacting bradykinin antagonists for a wide range of applications. Can J Physiol Pharmacol 75(6):719–724

    CAS  PubMed  Google Scholar 

  • Stone O, Richer C, Emanueli C et al (2009) Critical role of tissue kallikrein in vessel formation and maturation: implications for therapeutic revascularization. Arterioscler Thromb Vasc Biol 29(5):657–664

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sutera S, Chang K, Marvel J, Williamson J (1992) Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil. Am J Physiol 263(3 Pt 2):H945–950

    CAS  PubMed  Google Scholar 

  • Takagi C, Bursell S, Lin Y, Takagi H, Duh E, Jiang Z, Clermont A, King G (1996) Regulation of retinal hemodynamics in diabetic rats by increased expression and action of endothelin-1. Invest Ophthalmol Vis Sci 37(12):2504–2518

    CAS  PubMed  Google Scholar 

  • Takagi C, King G, Clermont A, Cummins D, Takagi H, Bursell S (1995) Reversal of abnormal retinal hemodynamics in diabetic rats by acarbose, an aglucosidase inhibitor. Curr Eye Res 14(9):741–749

    CAS  PubMed  Google Scholar 

  • Takeda H, Kimura Y, Higashida H, Yokoyama S (1999) Localization of B2 bradykinin receptor mRNA in the rat retina and sclerocornea. Immunopharmacology 45(1):51–55

    CAS  PubMed  Google Scholar 

  • Tarr J, Kaul K, Chopra M, Kohner E, Chibber R (2013) Pathophysiology of diabetic retinopathy. ISRN Ophthalmol 343560:1–13

    Google Scholar 

  • Thuringer D, Maulon L, Frelin C (2002) Rapid transactivation of the vascular endothelial growth factor receptor KDR/Flk-1 by the bradykinin B2 receptor contributes to endothelial nitric-oxide synthase activation in cardiac capillary endothelial cells. J Biol Chem 277(3):2028–2032

    CAS  PubMed  Google Scholar 

  • Tilton R, Chang K, Pugliese G, Eades D, Province M, Sherman W, Kilo C, Williamson J (1989) Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes 38(10):1258–1270

    CAS  PubMed  Google Scholar 

  • Tolentino M, Brucker A, Fosnot J, Ying G, Wu I, Malik G, Wan S, Reich S (1996) Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal neovascularization. Retina 24(1):132–138

    Google Scholar 

  • Tseng J, Vance S, Della T, Mendonca L, Cooney M, Klancnik J, Sorenson J, Freund K (2012) Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. J Glaucoma 21(4):241–247

    PubMed  Google Scholar 

  • Vincent J, Mohr S (2007) Inhibition of caspase-1/interleukin-1beta signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes 56(1):224–230

    CAS  PubMed  Google Scholar 

  • Wang J, Krishnamoorthi V, Wang E, Yang C, Baptista D, Wu X, Liu M, Gardner M, Elkins P, Hines J, Liu P (2010) LC/MS characterization of impurities and degradation products of a potent antitumor peptidic dimer, CU201. J Pharm Biomed Anal 51(4):824–833

    CAS  PubMed  Google Scholar 

  • Webb J (2011) The kallikrein/kinin system in ocular function. J Ocul Pharmacol Ther 27(6):539–543

    CAS  PubMed  Google Scholar 

  • Webb J, Husain S, Yates P, Crosson C (2006) Kinin modulation of conventional outflow facility in the bovine eye. J Ocul Pharmacol Ther 22(5):310–316

    CAS  PubMed  Google Scholar 

  • Whalley E, Figueroa C, Gera L, Bhoola K (2012) Discovery and therapeutic potential of kinin receptor antagonists. Expert Opin Drug Discov 7(12):1129–1148

    CAS  PubMed  Google Scholar 

  • Wilkinson-Berka J (2006) Angiotensin and diabetic retinopathy. Int J Biochem Cell Biol 38(5–6):752–765

    CAS  PubMed  Google Scholar 

  • Wirostko B, Wong T, Simo R (2008) Vascular endothelial growth factor and diabetic complications. Prog Retin Eye Res 27(6):608–621

    CAS  PubMed  Google Scholar 

  • Wirth K, Hock F, Albus U, Linz W, Alpermann H, Anagnostopoulos H, Henke S, Breipohl G, Konig W, Knolle J, Scholkens B (1991) Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies. Br J Pharmacol 102:774–777

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yao Y, Yin H, Shen B, Smith R, Liu Y, Gao L, Chao L, Chao J (2008) Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3beta pathway. Cardiovasc Res 80(3):354–364

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yermakova A, O’Banion M (2000) Cyclooxygenases in the central nervous system: implications for treatment of neurological disorders. Curr Pharm Des 6(17):1755–1776

    CAS  PubMed  Google Scholar 

  • Yoshida A, Feke G, Morales-Stoppello J, Collas G, Goger D, McMeel J (1983) Retinal blood flow alterations during progression of diabetic retinopathy. Arch Ophthalmol 101(2):225–227

    CAS  PubMed  Google Scholar 

  • Zheng L, Du Y, Miller C, Gubitosi-Klug R, Ball S, Berkowitz B, Kern T (2007) Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes. Diabetologia 50(9):1987–1996

    CAS  PubMed  Google Scholar 

  • Zuccollo A, Navarro M, Catanzaro O (1996) Effects of B1 and B2 kinin receptor antagonists in diabetic mice. Can J Physiol Pharm 74(5):586–589

    CAS  Google Scholar 

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Acknowledgments

Authors acknowledge the financial support of The Canadian Institutes of Health Research (CIHR, MOP-125962), the FRQS Vision Research Network, and the Foundation for Fighting Blindness. Authors are thankful to Dr Sébastien Olivier for providing ocular coherent tomography photographs and the critical review of the clinical management of diabetic retinopathy, Dr Sébastien Talbot for the measurement of B1R mRNA expression in human retinae and Mrs Micheline P. Gloin for the Artwork. Authors are also thankful to the donors and their family for providing the retina tissues for this study.

Competing Interests The authors declare that they have no conflict of interest.

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  1. École d’optométrie, Université de Montréal, CP 6128 Succursale centre-ville, Montréal, QC, H3C 3J7, Canada

    Menakshi Bhat, Mylène Pouliot & Elvire Vaucher

  2. Département de Physiologie moléculaire et intégrative, Université de Montréal, CP 6128 Succursale centre-ville, Montréal, QC, H3C 3J7, Canada

    Menakshi Bhat, Mylène Pouliot & Réjean Couture

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  1. Menakshi Bhat
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  2. Mylène Pouliot
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  3. Réjean Couture
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  4. Elvire Vaucher
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Correspondence to Elvire Vaucher .

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  1. Health Sciences Center, Faculty of Pharmacy, Department of Pharmacology and Therapeutics, Kuwait University, Safat, Kuwait

    Jagdish N. Sharma

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© 2014 Springer International Publishing Switzerland

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Bhat, M., Pouliot, M., Couture, R., Vaucher, E. (2014). The Kallikrein-Kinin System in Diabetic Retinopathy. In: Sharma, J. (eds) Recent Developments in the Regulation of Kinins. Progress in Drug Research, vol 69. Springer, Cham. https://doi.org/10.1007/978-3-319-06683-7_5

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