The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration.
The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration.
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DOI：
10.1371/journal.pone.0097302
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hernández C
中科院分区：
文献类型：
--
作者：
Bogdanov P;Corraliza L;Villena JA;Carvalho AR;Garcia-Arumí J;Ramos D;Ruberte J;Simó R;Hernández C
描述自发性2型糖尿病小鼠模型（db/db小鼠）视网膜神经变性中发生的顺序事件。以C57BLKsJ-db/db小鼠为自发性2型糖尿病动物模型，C57BLKsJ-db/+小鼠为对照组。为了评估异常的时间顺序，在不同的年龄（8、16和24周）进行了分析。通过视网膜电图（ERG）来评估视网膜的形态和功能异常。免疫组化评价神经退行性变的组织学指标（胶质细胞活化和凋亡）。此外，评估谷氨酸水平和谷氨酸/天冬氨酸转运蛋白（GLAST）表达。此外，为了确定与早期糖尿病视网膜病变相关的基因表达变化，在8周时进行转录组分析。此外，还进行了另一项降低血糖水平的介入性研究。糖尿病小鼠的神经胶质细胞活性在各阶段均高于非糖尿病小鼠（p<0.01）。此外，在糖尿病小鼠中还观察到神经节细胞的进行性损失和神经视网膜厚度的显着减少。所有这些神经变性的组织学特征在第8周比第16周和第24周更不明显。糖尿病小鼠在第16周和第24周出现明显的ERG异常，但在第8周没有。此外，我们观察到糖尿病小鼠中谷氨酸的逐渐积累与谷氨酸last的早期下调有关。通过降低血糖水平可以消除形态学和ERG异常。最后，在第8周发现与神经传递和氧化应激相关的几个基因如UCP2的失调。我们的研究结果表明，db/db小鼠再现了发生在人类糖尿病眼睛中的神经退行性过程的特征。因此，它似乎是研究糖尿病引起的视网膜神经变性的潜在机制和测试神经保护药物的合适模型。
To characterize the sequential events that are taking place in retinal neurodegeneration in a murine model of spontaneous type 2 diabetes (db/db mouse). C57BLKsJ-db/db mice were used as spontaneous type 2 diabetic animal model, and C57BLKsJ-db/+ mice served as the control group. To assess the chronological sequence of the abnormalities the analysis was performed at different ages (8, 16 and 24 weeks). The retinas were evaluated in terms of morphological and functional abnormalities [electroretinography (ERG)]. Histological markers of neurodegeneration (glial activation and apoptosis) were evaluated by immunohistochemistry. In addition glutamate levels and glutamate/aspartate transporter (GLAST) expression were assessed. Furthermore, to define gene expression changes associated with early diabetic retinopathy a transcriptome analyses was performed at 8 week. Furthermore, an additional interventional study to lower blood glucose levels was performed. Glial activation was higher in diabetic than in non diabetic mice in all the stages (p<0.01). In addition, a progressive loss of ganglion cells and a significant reduction of neuroretinal thickness were also observed in diabetic mice. All these histological hallmarks of neurodegeneration were less pronounced at week 8 than at week 16 and 24. Significant ERG abnormalities were present in diabetic mice at weeks 16 and 24 but not at week 8. Moreover, we observed a progressive accumulation of glutamate in diabetic mice associated with an early downregulation of GLAST. Morphological and ERG abnormalities were abrogated by lowering blood glucose levels. Finally, a dysregulation of several genes related to neurotransmission and oxidative stress such as UCP2 were found at week 8. Our results suggest that db/db mouse reproduce the features of the neurodegenerative process that occurs in the human diabetic eye. Therefore, it seems an appropriate model for investigating the underlying mechanisms of diabetes-induced retinal neurodegeneration and for testing neuroprotective drugs.
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影响因子：
4.4
作者：
Ju WK;Kim KY;Angert M;Duong-Polk KX;Lindsey JD;Ellisman MH;Weinreb RN
通讯作者：
Weinreb RN
生长抑素的局部给药可防止实验性糖尿病中的视网膜神经退行性。
影响因子：
7.7
作者：
Hernández C;García-Ramírez M;Corraliza L;Fernández-Carneado J;Farrera-Sinfreu J;Ponsati B;González-Rodríguez A;Valverde AM;Simó R
通讯作者：
Simó R
影响因子：
3.7
作者：
Feng, Yuxi;Wang, Yumei;Hammes, Hans-Peter
通讯作者：
Hammes, Hans-Peter
影响因子：
4.4
作者：
Barber, Alistair J.;Gardner, Thomas W.;Abcouwer, Steven F.
通讯作者：
Abcouwer, Steven F.
影响因子：
3.7
作者：
Feng, Yuxi;Wang, Yumei;Hammes, Hans-Peter
通讯作者：
Hammes, Hans-Peter