| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; the 3 National Research Center for Biotechnology, Braunschweig, Germany; the 4 Department of Pathology, Haartman Institute, Helsinki, Finland; and the 2 Lens and Cornea Research Unit, the Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands.
PURPOSE. The vascular endothelial growth factor (VEGF) family is involved in vascular leakage and angiogenesis in diabetic retinopathy (DR) in the eye, but may also have physiological functions. Based on the hypothesis that differential VEGF receptor (VEGFR) expression in the retina is an important determinant of effects of VEGF, this study was conducted to investigate VEGFR expression in the diabetic retina and in an experimental monkey model of VEGF-A–induced retinopathy.
METHODS. In retinas of 27 eyes of diabetic donors, 18 eyes of nondiabetic control donors, and 4 monkey eyes injected with PBS or VEGF-A, expression patterns of VEGFR-1, -2, and -3 in relation to leaky microvessels, as identified by the marker pathologische anatomie Leiden-endothelium (PAL-E) were studied by immunohistochemistry.
RESULTS. In control human retinas and retinas of PBS-injected monkey eyes, all three VEGFRs were expressed in nonvascular areas, but only VEGFR-1 was constitutively expressed in retinal microvessels. In diabetic eyes, increased microvascular VEGFR-2 expression was found in association with PAL-E expression, whereas microvascular VEGFR-3 was present in a subset of PAL-E–positive cases. In VEGF-A–injected monkey eyes, VEGFR-1, -2, and -3 and PAL-E were expressed in retinal microvessels.
CONCLUSIONS. The VEGFR-1, -2, and -3 expression patterns in control retinas suggest physiological functions of VEGFs that do not involve the vasculature. Initial vascular VEGF signaling may act primarily through VEGFR-1. In diabetic eyes, expression of retinal VEGFR-2 and -3 is increased, mainly in leaky microvessels, and VEGF-A induces vascular expression of the VEGF-A receptor VEGFR-2 and the VEGF-C/D receptor VEGFR-3. These findings indicate a dual role of VEGFs in the physiology and pathophysiology of the retina and suggest that microvascular VEGFR-2 and -3 signaling by VEGFs occurs late in the pathogenesis of DR, possibly initiated by high levels of VEGF-A in established nonproliferative DR.
This article has been cited by other articles:
|
|
 |
|
  E. J. Kuiper, J. M. Hughes, R. J. Van Geest, I. M. C. Vogels, R. Goldschmeding, C. J. F. Van Noorden, R. O. Schlingemann, and I. Klaassen Effect of VEGF-A on Expression of Profibrotic Growth Factor and Extracellular Matrix Genes in the Retina Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4267 - 4276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhao, G. Smith, J. Cai, A. Ma, and M. Boulton Vascular endothelial growth factor C promotes survival of retinal vascular endothelial cells via vascular endothelial growth factor receptor-2 Br. J. Ophthalmol., April 1, 2007; 91(4): 538 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Chen and J. P. Walterscheid Plaque Angiogenesis Versus Compensatory Arteriogenesis in Atherosclerosis Circ. Res., October 13, 2006; 99(8): 787 - 789. [Full Text] [PDF]
|
|
|
|
 |
|
 S. X Zhang, J. J Wang, G. Gao, K. Parke, and J.-x. Ma Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J. Mol. Endocrinol., August 1, 2006; 37(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Baffert, T. Le, B. Sennino, G. Thurston, C. J. Kuo, D. Hu-Lowe, and D. M. McDonald Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H547 - H559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E J Kuiper, A N Witmer, I Klaassen, N Oliver, R Goldschmeding, and R O Schlingemann Differential expression of connective tissue growth factor in microglia and pericytes in the human diabetic retina Br. J. Ophthalmol., August 1, 2004; 88(8): 1082 - 1087. [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]
|
|
|
|
 |
|
 A. N. Witmer, B. C. van Blijswijk, C. J.F. van Noorden, G. F.J.M. Vrensen, and R. O. Schlingemann In Vivo Angiogenic Phenotype of Endothelial Cells and Pericytes Induced by Vascular Endothelial Growth Factor-A J. Histochem. Cytochem., January 1, 2004; 52(1): 39 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Frank Diabetic Retinopathy N. Engl. J. Med., January 1, 2004; 350(1): 48 - 58. [Full Text] [PDF]
|
|
|
|
|
|
U. Schmidt-Erfurth, U. Schlotzer-Schrehard, C. Cursiefen, S. Michels, A. Beckendorf, and G. O. H. Naumann Influence of Photodynamic Therapy on Expression of Vascular Endothelial Growth Factor (VEGF), VEGF Receptor 3, and Pigment Epithelium-Derived Factor Invest. Ophthalmol. Vis. Sci., October 1, 2003; 44(10): 4473 - 4480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Orecchia, P. M. Lacal, C. Schietroma, V. Morea, G. Zambruno, and C. M. Failla Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the {alpha}5{beta}1 integrin J. Cell Sci., September 1, 2003; 116(17): 3479 - 3489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Witmer, J. Dai, H. A. Weich, G. F.J.M. Vrensen, and R. O. Schlingemann Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia J. Histochem. Cytochem., June 1, 2002; 50(6): 767 - 778. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
