Pigment epithelium-derived factor (PEDF) prevents diabetes- or advanced glycation end products (AGE)-elicited retinal leukostasis
Pigment epithelium-derived factor (PEDF) prevents diabetes- or advanced glycation end products (AGE)-elicited retinal leukostasis
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DOI：
10.1016/j.mvr.2006.04.002
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发表时间：
2006-07-01
影响因子：
3.1
通讯作者：
Imaizumi, Tsutomu
中科院分区：
文献类型：
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作者：
Yamagishi, Sho-Ichi;Matsui, Takanoni;Imaizumi, Tsutomu
色素上皮衍生因子（PEDF）是哺乳动物眼睛中最有效的血管生成抑制剂，表明PEDF可能对增殖性糖尿病视网膜病变有保护作用。然而，PEDF在早期糖尿病视网膜病变中的作用仍有待阐明。白细胞对视网膜毛细血管内皮的粘附（白细胞停滞）是早期糖尿病视网膜病变的关键事件，其过程主要由细胞间粘附分子-1 （ICAM-1）介导。我们在这里研究了PEDF是否可以通过抑制ICAM-1的表达来预防糖尿病或晚期糖基化终产物（AGE）引起的视网膜白质停滞。氧化应激标志物8-羟基脱氧鸟苷（8-OHdG）免疫组化结果显示，链脲佐菌素诱导的糖尿病大鼠视网膜内、外网状层细胞核呈强染色。给药PEDF或吡哆醛磷酸（一种AGE抑制剂）降低糖尿病大鼠视网膜8-OHdG水平，随后抑制ICAM-1基因表达和视网膜白质停滞。此外，正常大鼠静脉注射AGE增加了ICAM-1基因表达和视网膜白斑，这是由PEDF阻断的。PEDF还通过抑制ICAM-1的表达来抑制age诱导的T细胞对微血管内皮细胞的粘附。这些结果表明，PEDF通过抑制ICAM-1抑制糖尿病或age引起的视网膜白质停滞。我们目前的研究表明，PEDF可能通过减轻AGE的有害作用而对早期糖尿病视网膜病变起保护作用。(c) 2006爱思唯尔公司版权所有。
Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. Leukocyte adhesion to retinal capillary endothelium (leukostasis) is a critical event in early diabetic retinopathy, whose process is mainly mediated by intercellular adhesion molecule-1 (ICAM-1). We investigated here whether PEDF could prevent diabetes- or advanced glycation end products (AGE)-elicited retinal leukostasis by suppressing ICAM-1 expression. Immunohistochemistry of 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, showed intense staining in the nuclei of cells in the inner and outer plexiform layers of streptozotocin-induced diabetic rat retinas. Administration of PEDF or pyridoxal phosphate, an AGE inhibitor, decreased retinal levels of 8-OHdG and subsequently suppressed ICAM-1 gene expression and retinal leukostasis in diabetic rats. Further, intravenous administration of AGE to normal rats increased ICAM-1 gene expression and retinal leukostasis, which were blocked by PEDF. PEDF also inhibited the AGE-induced T cell adhesion to microvascular endothelial cells by suppressing ICAM-1 expression. These results demonstrated that PEDF inhibited diabetes- or AGE-elicited retinal leukostasis by suppressing ICAM-1. Our present study suggests that PEDF may play a protective role against early diabetic retinopathy by attenuating the deleterious effect of AGE. (c) 2006 Elsevier Inc. All rights reserved.