Diabetic Patients and Retinal Proliferation: An Evaluation of the Role of Vascular Endothelial Growth Factor (VEGF)

V. G. Nicoletti; R. Nicoletti; N. Ferrara; G. Meli; M. Reibaldi; A. Reibaldi

doi:10.1055/s-2003-40465

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Exp Clin Endocrinol Diabetes 2003; 111(4): 209-214
DOI: 10.1055/s-2003-40465

Article

J. A. Barth Verlag in Georg Thieme Verlag Stuttgart · New York

Diabetic Patients and Retinal Proliferation: An Evaluation of the Role of Vascular Endothelial Growth Factor (VEGF)

V. G. Nicoletti¹ , R. Nicoletti² , N. Ferrara³ , G. Meli¹ , M. Reibaldi⁴ , A. Reibaldi²

¹Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, University of Catania, Catania, Italy
²Department of Surgical and Medical Specialties, Section of Ophthalmology, University of Catania, Catania, Italy
³Department of Molecular Oncology, Genentech, Inc., South San Francisco, California, USA
⁴Department of Surgical and Medical Specialties, Section of Ophthalmology. University of Bari, Bari, Italy

Abstract

Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. The aim of this study was to evaluate the concentration of VEGF in vitreous, aqueous and epiretinal membranes of diabetic and non-diabetic patients, with other pathological conditions requiring surgical intervention. Higher VEGF concentration were found in samples from the eyes of diabetic patients versus other pathologies as well as in epiretinal membranes versus the other eye compartments in diabetic patients. However, high VEGF levels were also found in retinal detachment and proliferative vitreoretinopathy of non-diabetic patients. We concluded that VEGF is produced locally and plays a fundamental, but not specific, role in diabetic retinal neovascularisation and proliferation.

Key words

VEGF - Diabetic retinopathy - retinal proliferation

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Referenzen

References

1 Aiello L P, Avery R L, Arrigg P G, Keyt B A, Jampel H D, Shah S T, Pasquale L R, Thieme H, Iwamoto M A, Park J E. et al . Vascular endothelial growth factor in ocular fluid of patient with diabetic retinopathy and other retinal disorders. New Engl J Med. 1994; 331 1480-1487
2 Aiello L P, Cahill M T, Wong J S. Systemic considerations in the management of diabetic retinopathy. Am J Ophthalm. 2001; 132 760-776
3 Armstrong D, Augustin A J, Spengler R, Al-Jada A, Nickola T, Grus F, Koch F. Detection of vascular endothelial growth factor and tumor necrosis factor alpha in epiretinal membranes of proliferative diabetic retinopathy, proliferative vitreoretinopathy, and macular pucker. Ophtalmologica. 1998; 212 410-414
4 Borgstrom P, Bourdon M A, Hillan K J, Sriramarao P, Ferrara N. Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo. Prostate. 1998; 35 1-10
5 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001; 414 813-820
6 Chakrabarti S, Cukiernik M, Hileeto D, Evans T, Chen S. Role of vasoactive factors in the pathogenesis of early changes in diabetic retinopathy. Diabetes Metab Res Rev. 2000; 393-407
7 Chiarelli F, Santilli F, Mohn A. Role of growth factors in the development of diabetic complications. Horm Res. 2000; 53 53-67
8 Clarkson J G, Green W R, Massof D. A histopathologic review of 168 cases of preretinal membrane. Am J Ophthalmol. 1977; 84 1-17
9 Cross M J, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharm Sci. 2001; 22 201-207
10 Cooper M E, Bonnet F, Oldfield M, Jandeleit-Dahm K. Mechanisms of diabetic vasculopathy: an overview. Am J Hypertens. 2001; 14 475-486
11 Danis R, Massicotte S, Boldt C. Preretinal and optic nerve head neovascularization induced by photodynamic venous thrombosis in domestic pigs. Arch Ophthalmol. 1993; 111 539-543
12 Ferrara N. Molecular and biological properties of vascular endothelial growth factor. Metabolism. 1999; 48 1172-1178
13 Freyberger H, Brocker M, Yakut H, Hammer J, Effert R, Schifferdecker E, Schatz H, Derwahl M. Increased levels of pletelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy. Exp Clin Endocrinol Diabetes. 2000; 108 106-109
14 Gass J DR. In: Stereoscopic Atlas of Macular Disease: Diagnosis and Treatment. St. Louis; CV Mosby Co 1977: 344
15 Gaudric A, N'Guyen T, Moenner M, Glacet-Bernard A, Barritault D. Quantification of angiogenesis due to fibroblast growth factor in a modified rabbit corneal model. Ophthalmic Res. 1992; 24 181-188
16 Gengrinovitch S, Berman B, David G, Witte L, Neufeld G, Ron D. Glypican‐1 is a VEGF₁₆₅ binding proteoglycan that acts as an extracellular chaperone for VEGF₁₆₅. J Biol Chem. 1999; 274 10816-10822
17 Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G. Neuropilin-2 and neuropilin-1 are receptors for the 165-amino acid form of vascular endothelial growth factor (VEGF) and of placenta growth factor-2, but only neuropilin-2 functions as receptor for the 145-amino acid form of VEGF. J Biol Chem. 2000; 275 18040-18045
18 Gluzman-Poltorak Z, Cohen T, Shibuya M, Neufeld G. Vascular endothelial growth factor receptor-1 and neuropilin-2 form complexes. J Biol Chem. 2001; 276 18688-18694
19 Greene D A, Lattimer S A, Sima A A. Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications. N Engl J Med. 1987; 316 599-606
20 Katsura Y, Okano T, Noritake M, Kosano H, Nishigori H, Kado S, Matsuoka T. Hepatocyte growth factor in vitreous fluid of patients with proliferative diabetic retinopathy and other retinal disorders. Diabetes Care. 1998; 21 1759-1763
21 Kim J K, Li B, Winer J, Armanini M, Gillett N, Phillips H S, Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature. 1993; 362 841-844
22 Lu M, Kuroki M, Amano S, Tolentino M, Keough K, Kim I, Bucala R, Adamis A P. Advanced glycation end products increase retinal vascular endothelial growth factor expression. J Clin Invest. 1998; 101 1219-1224
23 Malecaze F, Clamens S, Simorre-Pinatel V, Mathis A, Chollet P, Favard C, Bayard F, Plouet J. Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophtalmol. 1994; 112 1476-1482
24 Nakagawa K, Chen Y X, Ishibashi H, Yonemitsu Y, Murata T, Hata Y, Nakashima Y, Sueshi K. Angiogenesis and its regulation: roles of vascular endothelial cell growth factor. Semin Thromb Hemost. 2000; 26 61-66
25 Paques M, Massin P, Gaudric A. Growth factors and diabetic retinopathy. Diabetes & Metabolism. 1997; 23 125-130
26 Joussen A M, Poulaki V, Qin W, Kirchhof B, Mitsiades N, Wiegand S J, Rudge J, Yancopoulos G D, Adamis A P. Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo. Am J Pathol. 2002; 160 501-509
27 Hammes H P, Lin J, Bretzel R G, Brownlee M, Breier G. Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. Diabetes. 1998; 47 401-406
28 Pe'er J, Folberg R, Itin A, Gnessin H, Hemo I, Keshet E. Upregulates expression of vascular endothelial growth factor in proliferative diabetic retinopathy. Br J Ophthalmol. 1996; 80 241-245
29 Pierce E A, Foley E D, Aiello L P, Smith L E. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci USA. 1995; 91 905-909
30 Risau W. Mechanisms of angiogenesis. Nature. 1997; 386 671-674
31 Rivard A, Berthou-Soulie L, Principe N, Kearney M, Curry C, Branellec D, Semenza G L, Isner J M. Age dependent defect in vascular endothelial growth factor expression is associated with reduced hypoxia-inducible factor 1 activity. J Biol Chem. 2000; 275 29643-29647
32 Robbins S G, Mixon R N, Wilson D J. et al . Platelet derived growth factor ligands and receptors immunolocalized in proliferative retinal disease. Invest Ophthalmol Vis Sci. 1994; 35 3649-3663
33 Shen B Q, Lee D Y, Gerber H P, Keyt B A, Ferrara N, Zioncheck T F. Homologous up-regulation of KDR/Flk-1 receptor expression by vascular endothelial growth factor in vitro. J Biol Chem. 1998; 273 29979-29985
34 Shepro D, Morel N M. Pericyte physiology. FASEB J. 1993; 7 1031-1038
35 Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001; 44 129-146
36 Spranger J, Pfeiffer A F. New concepts in pathogenesis and treatment of diabetic retinopathy. Exp Clin Endocrinol Diabetes. 2001; 109 (Suppl 2) S438-450
37 Wells J A, Murthy R, Chibber R, Nunn A, Molinatti P A, Kohner E M, Gregor Z J. Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation. Br J Ophthalmol. 1996; 80 363-366
38 Yamagishi S, Yonekura H, Yamamoto Y, Katsuno K, Sato F, Mita I, Ooka H, Satozawa N, Kawakami T, Nomura and Yamamoto M H. Advanced glycation end products-driven angiogenesis in vitro. Induction of the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor. J Biol Chem. 1997; 272 8723-8730

Prof. Alfredo Reibaldi

Department of Surgical and Medical Specialties
Section of Ophthalmology
University of Catania

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Italy

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