Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy
Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy
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DOI：
10.1172/jci118746
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发表时间：
1996-06-15
影响因子：
15.9
通讯作者：
Lorenzi, M
中科院分区：
文献类型：
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作者：
Mizutani, M;Kern, TS;Lorenzi, M
为了重建糖尿病视网膜病变转变为缺血性视网膜病变的血管闭塞机制，我们比较了糖尿病和非糖尿病个体视网膜微血管原位细胞死亡的发生率。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）反应研究了7例9 +/-4岁糖尿病患者（年龄67 +/-7岁）和8例年龄和性别匹配的非糖尿病对照者的视网膜胰蛋白酶切片和切片，该反应优先检测凋亡DNA片段。糖尿病患者视网膜微血管中TUNEL（+）细胞核总数（13 +/-12/1/6视网膜）显著高于对照组（1.3 +/-1.4，P = 0.0016），TUNEL（+）周细胞和内皮细胞计数也是如此（P < 0.006）。糖尿病和非糖尿病受试者的神经视网膜均为TUNEL（-）。实验性糖尿病或半乳糖血症持续时间较短且视网膜病变无或轻微形态学改变的大鼠的视网膜微血管显示TUNEL（+）周细胞和内皮细胞，而对照组大鼠则无。这些发现表明：（a）糖尿病和半乳糖血症导致视网膜周细胞和内皮细胞的原位加速死亡;（B）该事件是血管细胞特有的;（c）它先于视网膜病变的组织学证据;（d）它可以由孤立的高己糖血症诱导。内皮细胞的加速死亡和更新的循环可能导致血管结构的变化，并且在复制寿命耗尽时导致毛细血管闭塞。
To reconstruct the mechanisms for the vasoobliteration that transforms diabetic retinopathy into an ischemic retinopathy, we compared the occurrence of cell death in situ in retinal microvessels of diabetic and nondiabetic individuals. Trypsin digests and sections prepared from the retinas of seven patients (age 67 +/- 7 yr) with 9 +/- 4 yr of diabetes and eight age- and sex-matched nondiabetic controls were studied with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction which detects preferentially apoptotic DNA fragmentation. The count of total TUNEL(+) nuclei was significantly greater in the microvessels of diabetic (13 +/- 12 per one-sixth of retina) than control subjects (1.3 +/- 1.4, P = 0.0016), as were the counts of TUNEL(+) pericytes and endothelial cells (P < 0.006). The neural retinas from both diabetic and nondiabetic subjects were uniformly TUNEL(-). Retinal microvessels of rats with short duration of experimental diabetes or galactosemia and absent or minimal morphological changes of retinopathy, showed TUNEL(+) pericytes and endothelial cells, which were absent in control rats. These findings indicate that (a) diabetes and galactosemia lead to accelerated death in situ of both retinal pericytes and endothelial cells; (b) the event is specific for vascular cells; (c) it precedes histological evidence of retinopathy; and (d) it can be induced by isolated hyperhexosemia. A cycle of accelerated death and renewal of endothelial cells may contribute to vascular architectural changes and, upon exhaustion of replicative life span, to capillary obliteration.