Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina.
PLoS One. 2012;7(12):e51966. doi: 10.1371/journal.pone.0051966. Epub 2012 Dec 20.
Diabetic retinopathy is a leading cause of blindness. Visual function disorders have been demonstrated in diabetics even before the onset of retinopathy. At early stages of experimental diabetes, axoglial alterations occur at the distal portion of the optic nerve. Although ischemic conditioning can protect neurons and synaptic terminals against ischemic damage, there is no information on its ability to protect axons. We analyzed the effect of ischemic conditioning on the early axoglial alterations in the distal portion of the optic nerve induced by experimental diabetes. Diabetes was induced in Wistar rats by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mm Hg for 5 min; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. The application of ischemia pulses prevented a deficit in the anterograde transport from the retina to the superior colliculus, as well as an increase in astrocyte reactivity, ultraestructural myelin alterations, and altered morphology of oligodendrocyte lineage in the optic nerve distal portion at early stages of experimental diabetes. Ischemia tolerance prevented a significant decrease of retinal glutamine synthetase activity induced by diabetes. These results suggest that early vision loss in diabetes could be abated by ischemic conditioning which preserved axonal function and structure.
糖尿病性视网膜病变是失明的主要原因。即使在视网膜病变发生之前,糖尿病患者的视觉功能障碍也已经得到证实。在实验性糖尿病的早期阶段,视神经远端发生轴突胶质改变。虽然缺血预处理可以保护神经元和突触末端免受缺血性损伤,但关于其保护轴突的能力尚无信息。我们分析了缺血预处理对实验性糖尿病引起的视神经远端早期轴突胶质改变的影响。通过腹腔注射链脲佐菌素诱导 Wistar 大鼠发生糖尿病。通过将眼内压升高至 120mmHg 持续 5 分钟来诱导视网膜缺血;该操作在链脲佐菌素注射后 3 天开始,每周在一只眼重复一次,而对侧眼则进行假手术处理。缺血脉冲的应用可防止从视网膜到上丘的顺行转运缺陷,以及星形胶质细胞反应性、超微结构髓鞘改变和视神经远端少突胶质细胞谱系形态改变的增加,在实验性糖尿病的早期阶段。缺血耐受可预防糖尿病引起的视网膜谷氨酰胺合成酶活性显著降低。这些结果表明,通过缺血预处理可以减轻早期糖尿病引起的视力丧失,从而保持轴突的功能和结构。