AIMS/HYPOTHESIS: Monocytes and macrophages accumulate in the lesion of the diabetic retina, which are most likely involved in the progression of diabetic retinopathy. The levels of monocyte chemoattractant protein-1 (MCP-1) in vitreous fluids were associated with the severity of proliferative diabetic retinopathy. Recently, pigment epithelium-derived factor has been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, a role of pigment epithelium-derived factor in monocyte recruitments in diabetic retinopathy remains to be elucidated. In this study, we investigated effects of purified pigment epithelium-derived factor on AGE-induced reactive oxygen species generation, MCP-1 mRNA up-regulation and protein production in human cultured microvascular endothelial cells. METHODS: The intracellular formation of reactive oxygen species was measured using the fluorescent probe CM-H(2)DCFDA. MCP-1 gene expression was analysed in quantitative reverse transcription-polymerase chain reaction. Monocyte chemoattractant protein-1 production by microvascular endothelial cells was measured with an ELISA system. RESULTS: AGE increased intracellular reactive oxygen species generation in microvascular endothelial cells. Pigment epithelium-derived factor inhibited the AGE-induced reactive oxygen species generation in a dose-dependent manner. An anti-oxidant, N-acetylcysteine, or pigment epithelium-derived factor completely prevented the AGE-induced up-regulation of MCP-1 mRNA contents as well as protein production in microvascular endothelial cells. CONCLUSIONS/INTERPRETATIONS: Pigment epithelium-derived factor inhibits the AGE-induced reactive oxygen species generation and the subsequent increase in MCP-1 production in microvascular endothelial cells. Our study suggests that substitution of pigment epithelium-derived factor could prevent the progression of diabetic retinopathy by attenuating the deleterious effects of AGE.
AIMS/HYPOTHESIS: Monocytes and macrophages accumulate in the lesion of the diabetic retina, which are most likely involved in the progression of diabetic retinopathy. The levels of monocyte chemoattractant protein-1 (MCP-1) in vitreous fluids were associated with the severity of proliferative diabetic retinopathy. Recently, pigment epithelium-derived factor has been shown to be involved in the pathogenesis of proliferative diabetic retinopathy. However, a role of pigment epithelium-derived factor in monocyte recruitments in diabetic retinopathy remains to be elucidated. In this study, we investigated effects of purified pigment epithelium-derived factor on AGE-induced reactive oxygen species generation, MCP-1 mRNA up-regulation and protein production in human cultured microvascular endothelial cells. METHODS: The intracellular formation of reactive oxygen species was measured using the fluorescent probe CM-H(2)DCFDA. MCP-1 gene expression was analysed in quantitative reverse transcription-polymerase chain reaction. Monocyte chemoattractant protein-1 production by microvascular endothelial cells was measured with an ELISA system. RESULTS: AGE increased intracellular reactive oxygen species generation in microvascular endothelial cells. Pigment epithelium-derived factor inhibited the AGE-induced reactive oxygen species generation in a dose-dependent manner. An anti-oxidant, N-acetylcysteine, or pigment epithelium-derived factor completely prevented the AGE-induced up-regulation of MCP-1 mRNA contents as well as protein production in microvascular endothelial cells. CONCLUSIONS/INTERPRETATIONS: Pigment epithelium-derived factor inhibits the AGE-induced reactive oxygen species generation and the subsequent increase in MCP-1 production in microvascular endothelial cells. Our study suggests that substitution of pigment epithelium-derived factor could prevent the progression of diabetic retinopathy by attenuating the deleterious effects of AGE.
Authors: J Spranger; M Osterhoff; M Reimann; M Möhlig; M Ristow; M K Francis; V Cristofalo; H P Hammes; G Smith; M Boulton; A F Pfeiffer Journal: Diabetes Date: 2001-12 Impact factor: 9.461
Authors: Elia J Duh; Hoseong S Yang; Izumi Suzuma; Masaru Miyagi; Elaine Youngman; Keisuke Mori; Miyuki Katai; Lin Yan; Kiyoshi Suzuma; Karen West; Shekar Davarya; Patrick Tong; Peter Gehlbach; Joel Pearlman; John W Crabb; Lloyd P Aiello; Peter A Campochiaro; Donald J Zack Journal: Invest Ophthalmol Vis Sci Date: 2002-03 Impact factor: 4.799
Authors: F C Barouch; K Miyamoto; J R Allport; K Fujita; S E Bursell; L P Aiello; F W Luscinskas; A P Adamis Journal: Invest Ophthalmol Vis Sci Date: 2000-04 Impact factor: 4.799
Authors: S i Yamagishi; H Yonekura; Y Yamamoto; K Katsuno; F Sato; I Mita; H Ooka; N Satozawa; T Kawakami; M Nomura; H Yamamoto Journal: J Biol Chem Date: 1997-03-28 Impact factor: 5.157
Authors: Deepu R Pillai; Nagesh C Shanbhag; Michael S Dittmar; Ulrich Bogdahn; Felix Schlachetzki Journal: J Cereb Blood Flow Metab Date: 2013-01-09 Impact factor: 6.200