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. 2011;6(8):e23763. doi: 10.1371/journal.pone.0023763. Epub 2011 Aug 24.
Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning) on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS) in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i) intraocular pressure (IOP), ii) retinal function (electroretinogram (ERG)), iii) visual pathway function (visual evoked potentials, (VEPs)) iv) histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.
青光眼是导致后天性失明的主要原因之一，其可能涉及对视网膜神经节细胞和视神经头部的类似缺血性损伤。我们研究了每周应用短暂缺血脉冲（缺血预处理）对实验性青光眼引起的大鼠视网膜损伤的影响。通过每周在大鼠眼前房注射硫酸软骨素（CS）来诱导青光眼。通过将眼内压升高至 120mmHg 持续 5 分钟来诱导视网膜缺血；该操作在注射载体或 CS 后 6 周开始，并每周在一只眼重复一次，而对侧眼则进行假手术处理。青光眼通过以下指标进行评估：i）眼内压（IOP），ii）视网膜功能（视网膜电图（ERG）），iii）视觉通路功能（视觉诱发电位（VEPs）），iv）视网膜和视神经头部的组织学。视网膜硫代巴比妥酸物质水平被评估为脂质过氧化的指标。缺血预处理显著保护了 ERG、VEPs 以及视网膜和视神经头部结构免受青光眼损伤，而 IOP 没有变化。此外，缺血脉冲消除了实验性青光眼引起的脂质过氧化增加。这些结果表明，诱导缺血耐受可能为开发治疗青光眼的新治疗策略提供一个有前途的途径。
