Diabetic Complications Research Center, Division of Traditional Korean Medicine Integrated Research Korea Institute of Oriental Medicine, Daejeon, South Korea.
Ophthalmic Res. 2011;46(2):92-7. doi: 10.1159/000322809. Epub 2011 Jan 27.
Advanced glycation end products including Nε-(carboxymethyl)lysine (CML) are believed to contribute to retinal pericyte loss in diabetic retinopathy. Nuclear factor-κB (NF-κB) activation has been considered as a potential cytotoxic modulator of retinal pericytes. Herein, we investigated whether CML accumulation can trigger NF-κB activation and apoptosis of retinal pericytes in streptozotocin (STZ)-induced diabetic rats. Seven-week-old Sprague-Dawley rats were made diabetic (STZ, 60 mg/kg). After 5 months, CML level and NF-κB activation were measured in trypsin-digested retinal vessels. In diabetic rats, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive and caspase 3-positive retinal pericytes were significantly increased. CML and NF-κB activation was also markedly increased in diabetic retinal vessels. Moreover, the immunoreactivity of NF-κB was localized within the region where CML were accumulated. Apoptosis occurred in CML-accumulating retinal pericytes. These results suggest that NF-κB could be activated in CML-accumulating pericytes from diabetic retina. CML accumulation is responsible, at least in part, for the apoptosis of retinal pericytes.
晚期糖基化终产物，包括 Nε-（羧甲基）赖氨酸（CML），被认为是糖尿病性视网膜病变中视网膜周细胞丢失的原因之一。核因子-κB（NF-κB）的激活被认为是视网膜周细胞潜在的细胞毒性调节剂。在此，我们研究了 CML 积累是否可以触发链脲佐菌素（STZ）诱导的糖尿病大鼠视网膜周细胞的 NF-κB 激活和细胞凋亡。7 周龄的 Sprague-Dawley 大鼠被制成糖尿病（STZ，60mg/kg）。5 个月后，在胰蛋白酶消化的视网膜血管中测量 CML 水平和 NF-κB 激活。在糖尿病大鼠中，TUNEL（末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记）阳性和 caspase 3 阳性的视网膜周细胞明显增加。糖尿病视网膜血管中 CML 和 NF-κB 的激活也明显增加。此外，NF-κB 的免疫反应性定位于 CML 积累的区域内。凋亡发生在 CML 积累的视网膜周细胞中。这些结果表明，NF-κB 可在糖尿病视网膜中 CML 积累的周细胞中被激活。CML 积累至少部分导致了视网膜周细胞的凋亡。
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