Pigment Epithelium-derived Factor (PEDF) Blocks Advanced Glycation End Product (AGE)-induced Angiogenesis In Vitro

Introduction

Pigment epithelium-derived factor (PEDF) was first purified from the conditioned media of human retinal pigment epithelial cells with neuronal differentiating activity [1]. Recently, PEDF has been shown to be the most potent inhibitor of angiogenesis in the mammalian eye; it suppressed ischemia-induced retinal neovascularization [1]. These observations suggest that PEDF could protect against angiogenic eye disease such as proliferative diabetic retinopathy.

We, along with others, have shown that advanced glycation end products (AGEs), the senescent macroprotein derivatives, whose formation and accumulation occur at an accelerated rate in diabetes, are implicated in the development and progression of diabetic retinopathy as well [2] [3]. Indeed, AGEs could stimulate angiogenesis of cultured microvascular endothelial cells (ECs) by inducing autocrine production of vascular endothelial growth factor (VEGF), a key mediator of diabetic retinopathy [4]. In this study, we have investigated whether PEDF could inhibit the AGE-induced angiogenesis in vitro.

References

• 1 Tombran-Tink J, Barnstable CJ. Nat Rev Neurosci. 2003;  4 628-636
• 2 Yamagishi S, Imaizumi T. Curr Pharm Des. 2005;  11 2279-2299
• 3 Stitt AW, Frizzell N, Thorpe SR. Curr Pharm Des. 2004;  10 3349-3360
• 4 Okamoto T, Yamagishi S, Inagaki Y, Amano S, Koga K, Abe R, Takeuchi M, Ohno S, Yoshimura A, Makita Z. FASEB J. 2002;  16 1928-1930
• 5 Yamagishi S, Inagaki Y, Amano S, Okamoto T, Takeuchi M, Makita Z. Biochem Biophys Res Commun. 2002;  296 877-882
• 6 Takeuchi M, Watai T, Sasaki N, Choei H, Iwaki M, Ashizawa T, Inagaki Y, Yamagishi S, Kikuchi S, Riederer P, Saito T, Bucala R, Kameda Y. J Neuropathol Exp Neurol. 2003;  62 486-496
• 7 Yamagishi S, Inagaki Y, Okamoto T, Amano S, Koga K, Takeuchi M, Makita Z. J Biol Chem. 2002;  277 20309-20315
• 8 Yokoi M, Yamagishi SI, Takeuchi M, Ohgami K, Okamoto T, Saito W, Muramatsu M, Imaizumi T, Ohno S. Br J Ophthalmol. 2005;  89 673-675
• 9 Spranger J, Osterhoff M, Reimann M, Möhlig M, Ristow M, Francis MK, Cristofalo V, Hammes HP, Smith G, Boulton M, Pfeiffer AF. Diabetes. 2001;  50 2641-2645
• 10 Boehm BO, Lang G, Volpert O, Jehle PM, Kurkhaus A, Rosinger S, Lang GK, Bouck N. Diabetologia. 2003;  46 394-400

Correspondence