Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States.
Neurobiology Department, Northwestern University, Evanston, Illinois, United States.
Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):723-730. doi: 10.1167/iovs.18-26073.
The purpose of this study was to determine whether the ability of the rat retina to control its pH is affected by diabetes.
Double-barreled H+-selective microelectrodes were used to measure extracellular [H+] in the dark-adapted retina of intact control and diabetic Long-Evans rats 1 to 6 months after intraperitoneal injection of vehicle or streptozotocin, respectively. Two manipulations-increasing of blood glucose and intravenous injection of the carbonic anhydrase blocker dorzolamide (DZM)-were used to examine their effects on retinal pH regulation.
An increase of retinal acidity was correlated with the diabetes-related increase in blood glucose, but only between 1 and 3 months of diabetes, not earlier or later. Adding intravenous glucose had no noticeable effect on the retinal acidity of control animals. In contrast, similar injections of glucose in diabetic rats significantly increased the acidity of the retina. Again, the largest increase of retinal acidity due to artificially elevated blood glucose was observed at 1 to 3 months of diabetes. Suppression of carbonic anhydrase by DZM dramatically increased the retinal acidity in both control and diabetic retinas to a similar degree. However, in controls, the strongest effect of DZM was recorded within 10 minutes after the injection, but in diabetics, the effect tended to increase with time and after 2 hours could be two to three times larger than at the beginning.
During development of diabetes in rats, the control over retinal pH is partly compromised so that conditions that perturb retinal pH lead to larger and/or more sustained changes than in control animals.
本研究旨在确定糖尿病是否会影响大鼠视网膜控制其 pH 值的能力。
使用双腔 H+-选择性微电极在暗适应的完整对照和糖尿病 Long-Evans 大鼠的视网膜外液中测量 [H+],分别在腹腔注射载体或链脲佐菌素后 1 至 6 个月。两种操作——升高血糖和静脉注射碳酸酐酶抑制剂多佐胺(DZM)——用于检查它们对视网膜 pH 调节的影响。
视网膜酸度的增加与糖尿病相关的血糖升高相关,但仅在 1 至 3 个月的糖尿病期间,而不是更早或更晚。向对照动物静脉内注射葡萄糖对视网膜酸度没有明显影响。相比之下,在糖尿病大鼠中类似的葡萄糖注射显著增加了视网膜的酸度。同样,由于人为升高血糖导致的视网膜酸度最大增加发生在 1 至 3 个月的糖尿病期间。DZM 抑制碳酸酐酶可使对照和糖尿病视网膜的酸度均显著增加至相似程度。然而,在对照动物中,DZM 的最强作用在注射后 10 分钟内记录到,但在糖尿病动物中,作用随时间而增加,2 小时后可比开始时大 2 至 3 倍。
在大鼠糖尿病的发展过程中,对视网膜 pH 的控制部分受损,因此会导致比对照动物更大和/或更持续的变化。