Department of Anatomy, School of Basic Medical Sciences, Peking University, Beijing, China.
PLoS One. 2012;7(1):e30343. doi: 10.1371/journal.pone.0030343. Epub 2012 Jan 17.
The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice.
METHODOLOGY/PRINCIPAL FINDINGS: In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ON- and OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8 wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina.
CONCLUSIONS/SIGNIFICANCE: The altered visual functions of RGCs were characterized by the reduced RF center size, elevated LT, and attenuated contrast gain in 12 and 20 wk db/db mice, respectively. These altered visual functions could, at least partly, be due to oxidative stress since in vitro application of SOD effectively improves visual functions.
C57BLKS/J db/db（db/db）小鼠是一种广泛使用的 2 型糖尿病动物模型，该模型在 24 周时开始出现早期内视网膜神经元功能障碍。介导该模型早期视网膜功能障碍的神经机制尚不清楚。我们评估了 db/db 小鼠糖尿病早期（8、12 和 20 周）视网膜神经节细胞（RGC）的视觉反应特性，并确定在 20 周龄 db/db 小鼠中，氧化应激增加是否在 RGC 视觉功能受损中起作用。
方法/主要发现：在全视网膜培养物上进行了 RGC 的体外细胞外单细胞记录。研究了 RGC 的感受野大小、亮度阈值和对比增益。虽然 ON 和 OFF-RGC 表现出不同的 RF 大小减小的时间过程，但到 20 周时，ON 和 OFF-RGC 的 RF 受到类似的影响。与 OFF-RGC 的 LT 相比，12 周和 20 周 db/db 小鼠的 ON-RGC 的 LT 显著升高。糖尿病损伤也以不同的方式影响 ON 和 OFF-RGC 的对比增益。通过二氢乙啶估计新鲜视网膜中活性氧物种（ROS）的产生。超氧化物歧化酶（SOD）（300 单位/ml）应用于 Ames 培养基中的视网膜，并记录 RGC 的视觉反应五个小时。db/db 小鼠视网膜中的 ROS 生成在 8 周时增加，并在 20 周时继续进展。在体外用 SOD 处理可改善 20 周 db/db 小鼠的视觉功能，但 SOD 处理对 db/m 视网膜中的 ON 和 OFF-RGC 有不同的影响。
结论/意义：在 12 和 20 周 db/db 小鼠中，RGC 的视觉功能改变分别表现为 RF 中心大小减小、LT 升高和对比增益降低。这些改变的视觉功能至少部分归因于氧化应激，因为在体外用 SOD 可有效改善视觉功能。
