Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.
Department of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan.
Sci Rep. 2021 Sep 15;11(1):18401. doi: 10.1038/s41598-021-97651-3.
We investigated and compared the susceptibility of retinal blood flow regulation and neural function in mice developing type 2 diabetes. The longitudinal changes in retinal neuronal function and blood flow responses to a 10-min systemic hyperoxia and a 3-min flicker stimulation were evaluated every 2 weeks in diabetic db/db mice and nondiabetic controls (db/m) from age 8 to 20 weeks. The retinal blood flow and neural activity were assessed using laser speckle flowgraphy and electroretinography (ERG), respectively. The db/db mice had significantly higher blood glucose levels and body weight. The resting retinal blood flow was steady and comparable between two groups throughout the study. Hyperoxia elicited a consistent decrease, and flicker light an increase, in retinal blood flow in db/m mice independent of age. However, these flow responses were significantly diminished in db/db mice at 8 weeks old and then the mice became unresponsive to stimulations at 12 weeks. Subsequently, the ERG implicit time for oscillatory potential was significantly increased at 14 weeks of age while the a-wave and b-wave amplitudes and implicit times remained unchanged. The deficiencies of flow regulation and neurovascular coupling in the retina appear to precede neural dysfunction in the mouse with type 2 diabetes.
我们研究并比较了发生 2 型糖尿病的小鼠视网膜血流调节和神经功能的易感性。从 8 至 20 周龄，我们每隔 2 周评估糖尿病 db/db 小鼠和非糖尿病对照(db/m)的视网膜神经元功能和血流对 10 分钟全身高氧和 3 分钟闪烁刺激的纵向变化。使用激光散斑血流图和视网膜电图（ERG）分别评估视网膜血流和神经活动。db/db 小鼠的血糖水平和体重明显较高。在整个研究过程中，两组的静息视网膜血流保持稳定且相似。高氧刺激在 db/m 小鼠中引起一致的视网膜血流减少，闪烁光刺激引起增加，与年龄无关。然而，这些血流反应在 8 周龄的 db/db 小鼠中明显减弱，然后在 12 周时小鼠对刺激无反应。随后，在 14 周龄时，眼震性电位的 ERG 潜伏期显著增加，而 a 波和 b 波幅度和潜伏期保持不变。在 2 型糖尿病小鼠中，视网膜的血流调节和神经血管耦联缺陷似乎先于神经功能障碍。
