Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
Center for Translational Neuromedicine, University of Rochester Medical School, Elmwood Avenue 601, 14642, Rochester, NY, USA.
Fluids Barriers CNS. 2024 Mar 12;21(1):26. doi: 10.1186/s12987-024-00524-w.
Glymphatic transport is vital for the physiological homeostasis of the retina and optic nerve. Pathological alterations of ocular glymphatic fluid transport and enlarged perivascular spaces have been described in glaucomatous mice. It remains to be established how diabetic retinopathy, which impairs vision in about 50% of diabetes patients, impacts ocular glymphatic fluid transport. Here, we examined ocular glymphatic transport in chronic hyperglycemic diabetic mice as well as in healthy mice experiencing a daily transient increase in blood glucose. Mice suffering from severe diabetes for two and four months, induced by streptozotocin, exhibited no alterations in ocular glymphatic fluid transport in the optic nerve compared to age-matched, non-diabetic controls. In contrast, transient increases in blood glucose induced by repeated daily glucose injections in healthy, awake, non-diabetic mice accelerated antero- and retrograde ocular glymphatic transport. Structural analysis showed enlarged perivascular spaces in the optic nerves of glucose-treated mice, which were absent in diabetic mice. Thus, transient repeated hyperglycemic events, but not constant hyperglycemia, ultimately enlarge perivascular spaces in the murine optic nerve. These findings indicate that fluid transport in the mouse eye is vulnerable to fluctuating glycemic levels rather than constant hyperglycemia, suggesting that poor glycemic control drives glymphatic malfunction and perivascular enlargement in the optic nerve.
神经胶质淋巴转运对于视网膜和视神经的生理稳态至关重要。在青光眼小鼠中，已经描述了眼部神经胶质淋巴液转运的病理性改变和血管周围空间的扩大。糖尿病性视网膜病变会损害约 50%的糖尿病患者的视力，但它如何影响眼部神经胶质淋巴液转运仍有待确定。在这里，我们研究了慢性高血糖糖尿病小鼠以及经历每日短暂血糖升高的健康小鼠的眼部神经胶质淋巴转运。与年龄匹配的非糖尿病对照组相比，用链脲佐菌素诱导患有严重糖尿病 2 个月和 4 个月的小鼠，其视神经中的眼部神经胶质淋巴液转运没有改变。相比之下，在清醒的非糖尿病健康小鼠中，通过每日重复血糖注射引起的短暂血糖升高加速了前向和后向眼部神经胶质淋巴转运。结构分析显示，葡萄糖处理小鼠的视神经中血管周围空间扩大，而糖尿病小鼠中则没有。因此，反复短暂的高血糖事件，而不是持续的高血糖，最终会导致小鼠视神经中血管周围空间扩大。这些发现表明，小鼠眼睛中的液体转运易受血糖波动的影响，而不是持续的高血糖，这表明血糖控制不佳会导致视神经中的神经胶质功能障碍和血管周围扩大。
