Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock.
Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock.
复制标题
DOI：
10.1084/jem.20090889
复制
发表时间：
2009-12-21
期刊：
影响因子：
--
通讯作者：
Grant MB
中科院分区：
文献类型：
--
作者：
Busik JV;Tikhonenko M;Bhatwadekar A;Opreanu M;Yakubova N;Caballero S;Player D;Nakagawa T;Afzal A;Kielczewski J;Sochacki A;Hasty S;Li Calzi S;Kim S;Duclas SK;Segal MS;Guberski DL;Esselman WJ;Boulton ME;Grant MB
目前糖尿病的流行导致全世界心血管和微血管并发症（包括视网膜病变）的增加。目前的观点主要集中在视网膜的局部影响上，认为这是导致这种糖尿病并发症发生的原因。然而，循环细胞在脉管系统的维护、修复和功能障碍中的贡献现在越来越受到重视。糖尿病个体循环中的内皮祖细胞 (EPC) 较少，这些细胞的迁移潜力减弱，这导致其修复能力下降。使用 2 型糖尿病大鼠模型，我们发现糖尿病骨髓中 EPC 释放的减少是由骨髓神经病变引起的，并且这些变化先于糖尿病视网膜病变的发生。在患糖尿病 4 个月的大鼠中，我们观察到骨髓中神经末梢的数量急剧减少。去神经支配伴随着骨髓内EPC数量的增加，但循环中数量的减少。此外，去神经支配还伴随着EPC昼夜节律释放的丧失以及视网膜和EPC本身时钟基因表达的显着减少。 EPC 释放昼夜节律峰值的减少导致修复能力下降，从而导致糖尿病视网膜病变的标志性特征——无细胞视网膜毛细血管的形成。因此，糖尿病视网膜病变首次与骨髓神经病变相关。这一新发现表明骨髓去神经术代表了治疗糖尿病血管并发症的新治疗靶点。
The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution of circulating cells in maintenance, repair, and dysfunction of the vasculature is now becoming appreciated. Diabetic individuals have fewer endothelial progenitor cells (EPCs) in their circulation and these cells have diminished migratory potential, which contributes to their decreased reparative capacity. Using a rat model of type 2 diabetes, we show that the decrease in EPC release from diabetic bone marrow is caused by bone marrow neuropathy and that these changes precede the development of diabetic retinopathy. In rats that had diabetes for 4 mo, we observed a dramatic reduction in the number of nerve terminal endings in the bone marrow. Denervation was accompanied by increased numbers of EPCs within the bone marrow but decreased numbers in circulation. Furthermore, denervation was accompanied by a loss of circadian release of EPCs and a marked reduction in clock gene expression in the retina and in EPCs themselves. This reduction in the circadian peak of EPC release led to diminished reparative capacity, resulting in the development of the hallmark feature of diabetic retinopathy, acellular retinal capillaries. Thus, for the first time, diabetic retinopathy is related to neuropathy of the bone marrow. This novel finding shows that bone marrow denervation represents a new therapeutic target for treatment of diabetic vascular complications.
登录
查看更多内容
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
15.9
作者：
Mizutani, M;Kern, TS;Lorenzi, M
通讯作者：
Lorenzi, M
影响因子：
7.7
作者：
Segal, MS;Shah, R;Grant, MB
通讯作者：
Grant, MB
影响因子：
2.5
作者：
Tirabassi, RS;Flanagan, JF;Guberski, DL
通讯作者：
Guberski, DL
影响因子：
7.4
作者：
Ellis, EA;Grant, MB;Lutty, GA
通讯作者：
Lutty, GA