(Hypertension. 2000;36:1099.)
© 2000 American Heart Association, Inc.
Colin Johnston - A Celebration |
Retinal Neovascularization Is Prevented by Blockade of the Renin-Angiotensin System
From the Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia (C.J.M., S.L.S., J.L.W.-B.); the Department of Medicine, The University of Melbourne, St Vincents Hospital, Fitzroy, Victoria, Australia (D.J.K., R.E.G.); the Department of Medicine, The University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg West, Victoria, Australia (M.E.C.); the Department of Anatomy, Monash University, Clayton, Victoria, Australia (J.F.B.); and Merck Research Laboratories, Bluebell, Pa (S.S.).
Correspondence to Dr Jennifer L. Wilkinson-Berka, Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia, 3010. E-mail j.berka{at}physiology.unimelb.edu.au
Both angiotensin II and vascular endothelial growth factor are angiogenic agents that have recently been implicated in the pathogenesis of proliferative diabetic retinopathy. In this study, retinal neovascularization was examined in a model of retinopathy of prematurity with the use of neonatal transgenic (mRen-2)27 rats, which overexpress renin in tissues, and Sprague-Dawley rats. Blockers of the renin-angiotensin system were administered during the neovascularization period. The ACE inhibitor lisinopril and the angiotensin type 1 receptor antagonist losartan both increased retinal renin levels and prevented inner retinal blood vessel growth. Quantitative in situ hybridization revealed that the expression of vascular endothelial growth factor and its type 2 receptor in the inner retina and proliferating blood vessels were increased in rats with retinopathy of prematurity. Lisinopril reduced both retinal vascular endothelial growth factor and its type 2 receptor mRNA in retinopathy of prematurity rats, whereas losartan had no effect. It is predicted that agents that interrupt the renin-angiotensin system may play an important role as retinoprotective agents in various forms of proliferative retinopathy.
Key Words: renin\b • growth substances\b • angiotensin\b • renin-angiotensin system
This article has been cited by other articles:
 |
|
 |
|
  S. Satofuka, A. Ichihara, N. Nagai, K. Noda, Y. Ozawa, A. Fukamizu, K. Tsubota, H. Itoh, Y. Oike, and S. Ishida (Pro)renin Receptor-Mediated Signal Transduction and Tissue Renin-Angiotensin System Contribute to Diabetes-Induced Retinal Inflammation Diabetes, July 1, 2009; 58(7): 1625 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Okunuki, Y. Usui, N. Nagai, T. Kezuka, S. Ishida, M. Takeuchi, and H. Goto Suppression of Experimental Autoimmune Uveitis by Angiotensin II Type 1 Receptor Blocker Telmisartan Invest. Ophthalmol. Vis. Sci., May 1, 2009; 50(5): 2255 - 2261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Wilkinson-Berka, G. Tan, K. Jaworski, and A. G. Miller Identification of a Retinal Aldosterone System and the Protective Effects of Mineralocorticoid Receptor Antagonism on Retinal Vascular Pathology Circ. Res., January 2, 2009; 104(1): 124 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Wilkinson-Berka Prorenin and the (Pro)renin Receptor in Ocular Pathology Am. J. Pathol., December 1, 2008; 173(6): 1591 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. de Resende and A. S. Greene Effect of ANG II on endothelial cell apoptosis and survival and its impact on skeletal muscle angiogenesis after electrical stimulation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2814 - H2821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Connelly, D. Kelly, and R. Gilbert Clinically Relevant Models of Diabetic Cardiac Complications Circ. Res., September 14, 2007; 101(6): e78 - e78. [Full Text] [PDF]
|
|
|
|
|
|
N. Nagai, K. Izumi-Nagai, Y. Oike, T. Koto, S. Satofuka, Y. Ozawa, K. Yamashiro, M. Inoue, K. Tsubota, K. Umezawa, et al. Suppression of Diabetes-Induced Retinal Inflammation by Blocking the Angiotensin II Type 1 Receptor or Its Downstream Nuclear Factor-{kappa}B Pathway Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4342 - 4350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. deS. Senanayake, J. Drazba, K. Shadrach, A. Milsted, E. Rungger-Brandle, K. Nishiyama, S.-I. Miura, S. Karnik, J. E. Sears, and J. G. Hollyfield Angiotensin II and Its Receptor Subtypes in the Human Retina Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3301 - 3311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nagai, Y. Oike, K. Izumi-Nagai, T. Koto, S. Satofuka, H. Shinoda, K. Noda, Y. Ozawa, M. Inoue, K. Tsubota, et al. Suppression of Choroidal Neovascularization by Inhibiting Angiotensin-Converting Enzyme: Minimal Role of Bradykinin Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2321 - 2326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Phipps, J. L. Wilkinson-Berka, and E. L. Fletcher Retinal Dysfunction in Diabetic Ren-2 Rats Is Ameliorated by Treatment with Valsartan but Not Atenolol Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 927 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Satofuka, A. Ichihara, N. Nagai, T. Koto, H. Shinoda, K. Noda, Y. Ozawa, M. Inoue, K. Tsubota, H. Itoh, et al. Role of Nonproteolytically Activated Prorenin in Pathologic, but Not Physiologic, Retinal Neovascularization Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 422 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wilkinson-Berka, D. Jones, G. Taylor, K. Jaworski, D. J. Kelly, S. B. Ludbrook, R. N. Willette, S. Kumar, and R. E. Gilbert SB-267268, a Nonpeptidic Antagonist of {alpha}v{beta}3 and {alpha}v{beta}5 Integrins, Reduces Angiogenesis and VEGF Expression in a Mouse Model of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1600 - 1605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Silvestre and B. I. Levy Molecular Basis of Angiopathy in Diabetes Mellitus Circ. Res., January 6, 2006; 98(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
|
|
P. B. Bergman, C. J. Moravski, S. R. Edmondson, V. C. Russo, L. A. Bach, J. L. Wilkinson-Berka, and G. A. Werther Expression of the IGF System in Normal and Diabetic Transgenic (mRen-2)27 Rat Eye Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2708 - 2715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nagai, Y. Oike, K. Noda, T. Urano, Y. Kubota, Y. Ozawa, H. Shinoda, T. Koto, K. Shinoda, M. Inoue, et al. Suppression of Ocular Inflammation in Endotoxin-Induced Uveitis by Blocking the Angiotensin II Type 1 Receptor Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2925 - 2931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Yokota, F Mori, K Kai, T Nagaoka, N Izumi, A Takahashi, T Hikichi, A Yoshida, F Suzuki, and Y Ishida Serum prorenin levels and diabetic retinopathy in type 2 diabetes: new method to measure serum level of prorenin using antibody activating direct kinetic assay Br. J. Ophthalmol., July 1, 2005; 89(7): 871 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 The DIRECT Programme Study Group The DIabetic REtinopathy Candesartan Trials (DIRECT) Programme: baseline characteristics Journal of Renin-Angiotensin-Aldosterone System, March 1, 2005; 6(1): 25 - 32. [Abstract] [PDF]
|
|
|
|
|
|
S. Sarlos and J. L. Wilkinson-Berka The Renin-Angiotensin System and the Developing Retinal Vasculature Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 1069 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nagai, K. Noda, T. Urano, Y. Kubota, H. Shinoda, T. Koto, K. Shinoda, M. Inoue, T. Shiomi, E. Ikeda, et al. Selective Suppression of Pathologic, but Not Physiologic, Retinal Neovascularization by Blocking the Angiotensin II Type 1 Receptor Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 1078 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. G. Ebrahimian, R. Tamarat, M. Clergue, M. Duriez, B. I. Levy, and J.-S. Silvestre Dual Effect of Angiotensin-Converting Enzyme Inhibition on Angiogenesis in Type 1 Diabetic Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 65 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Toko, Y. Zou, T. Minamino, M. Sakamoto, M. Sano, M. Harada, T. Nagai, T. Sugaya, F. Terasaki, Y. Kitaura, et al. Angiotensin II Type 1a Receptor Is Involved in Cell Infiltration, Cytokine Production, and Neovascularization in Infarcted Myocardium Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 664 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wilkinson-Berka, S. Babic, T. de Gooyer, A. W. Stitt, K. Jaworski, L. G. T. Ong, D. J. Kelly, and R. E. Gilbert Inhibition of Platelet-Derived Growth Factor Promotes Pericyte Loss and Angiogenesis in Ischemic Retinopathy Am. J. Pathol., April 1, 2004; 164(4): 1263 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tikellis, M. E. Cooper, Stephen. M. Twigg, W. C. Burns, and M. Tolcos Connective Tissue Growth Factor Is Up-Regulated in the Diabetic Retina: Amelioration by Angiotensin-Converting Enzyme Inhibition Endocrinology, February 1, 2004; 145(2): 860 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, M. Lassila, M. E. Cooper, and Z. Cao Retinal Expression of Vascular Endothelial Growth Factor Is Mediated by Angiotensin Type 1 and Type 2 Receptors Hypertension, February 1, 2004; 43(2): 276 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Ciulla, A. G. Amador, and B. Zinman Diabetic Retinopathy and Diabetic Macular Edema: Pathophysiology, screening, and novel therapies Diabetes Care, September 1, 2003; 26(9): 2653 - 2664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sarlos, B. Rizkalla, C. J. Moravski, Z. Cao, M. E. Cooper, and J. L. Wilkinson-Berka Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin Am. J. Pathol., September 1, 2003; 163(3): 879 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kelly, C. Hepper, L. L. Wu, A. J. Cox, and R. E. Gilbert Vascular endothelial growth factor expression and glomerular endothelial cell loss in the remnant kidney model Nephrol. Dial. Transplant., July 1, 2003; 18(7): 1286 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Wilkinson-Berka, N. S. Alousis, D. J. Kelly, and R. E. Gilbert COX-2 Inhibition and Retinal Angiogenesis in a Mouse Model of Retinopathy of Prematurity Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 974 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Moravski, S. L. Skinner, A. J. Stubbs, S. Sarlos, D. J. Kelly, M. E. Cooper, R. E. Gilbert, and J. L. Wilkinson-Berka The Renin-Angiotensin System Influences Ocular Endothelial Cell Proliferation in Diabetes: Transgenic and Interventional Studies Am. J. Pathol., January 1, 2003; 162(1): 151 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W D. Strain and N. Chaturvedi Review: The renin-angiotensin-aldosterone system and the eye in diabetes Journal of Renin-Angiotensin-Aldosterone System, December 1, 2002; 3(4): 243 - 246. [Abstract] [PDF]
|
|
|
|
|
|
F Mori, T Hikichi, T Nagaoka, J Takahashi, N Kitaya, and A Yoshida Inhibitory effect of losartan, an AT1 angiotensin II receptor antagonist, on increased leucocyte entrapment in retinal microcirculation of diabetic rats Br. J. Ophthalmol., October 1, 2002; 86(10): 1172 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Abcouwer, P. L. Marjon, R. K. Loper, and D. L. Vander Jagt Response of VEGF Expression to Amino Acid Deprivation and Inducers of Endoplasmic Reticulum Stress Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2791 - 2798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Funatsu, H Yamashita, Y Nakanishi, and S Hori Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy Br. J. Ophthalmol., March 1, 2002; 86(3): 311 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Nadal, G. M. Scicli, L. A. Carbini, and A. G. Scicli Angiotensin II stimulates migration of retinal microvascular pericytes: involvement of TGF-beta and PDGF-BB Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H739 - H748. [Abstract] [Full Text] [PDF]
|
|