Neural apoptosis in the retina during experimental and human diabetes - Early onset and effect of insulin
Neural apoptosis in the retina during experimental and human diabetes - Early onset and effect of insulin
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DOI：
10.1172/jci2425
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发表时间：
1998-08-15
影响因子：
15.9
通讯作者：
Gardner, TW
中科院分区：
文献类型：
--
作者：
Barber, AJ;Lieth, E;Gardner, TW
本研究确定糖尿病视网膜变性是否包括视网膜神经细胞凋亡。对链脲佐菌素（STZ）糖尿病大鼠7.5个月后的视网膜切片进行图像分析，发现内网状层和内核层的厚度分别减少了22%和14%（P < 0.001）。与对照组相比，存活的神经节细胞的数量也减少了10%（P < 0.001）。DNA末端dUTP缺口末端标记（TUNEL）原位末端标记法证实糖尿病1、3、6和12个月后大鼠视网膜整体安装的视网膜细胞凋亡频率增加10倍（分别为P < 0.001、P < 0.001、P < 0.01和P < 0.01）。大多数TUNEL阳性细胞与血管无关，也不与内皮细胞特异性抗原血管性血友病因子共定位。胰岛素植入组TUNEL阳性细胞数明显减少（P < 0.05）。糖尿病患者视网膜中TUNEL阳性细胞的数量也增加。这些数据表明，视网膜神经细胞死亡发生在糖尿病早期。这是第一次定量报告糖尿病期间视网膜神经细胞凋亡增加，并表明神经变性是糖尿病视网膜病变的重要组成部分。
This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively (P < 0.001). The number of surviving ganglion cells was also reduced by 10% compared to controls (P < 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in whole-mounted rat retinas after 1, 3, 6, and 12 months of diabetes (P < 0.001, P < 0.001, P < 0.01, and P < 0.01, respectively). Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor. Insulin implants significantly reduced the number of TUNEL-positive cells (P < 0.05). The number of TUNEL-positive cells was also increased in retinas from humans with diabetes. These data indicate that retinal neural cell death occurs early in diabetes. This is the first quantitative report of an increase in neural cell apoptosis in the retina during diabetes, and indicates that neurodegeneration is an important component of diabetic retinopathy.