Sims Stephanie M, Holmgren Lauren, Cathcart Heather M, Sappington Rebecca M
Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA.
Am J Neurodegener Dis. 2012;1(2):168-79.
Neuroinflammation, defined as the induction of immune-related processes within the central nervous system, is recognized as a component of many neurodegenerative disorders, including glaucomatous degeneration of retinal ganglion cells (RGCs). Previous work in vitro identified IL-6 as a potential neuroprotective factor for RGCs, particularly those challenged by glaucoma-related stressors. Here we examined the temporal and spatial characteristics of IL-6 signaling in response to two stressors related to RGC neurodegeneration: age and elevated intraocular pressure (IOP). Using ELISA, immunoblotting, immunolabeling and quantitative microscopy, we measured and compared whole retina and RGC-related expression of IL-6 and IL-6Rα in normal retina (young C57), retina susceptible to glaucomatous neurodegeneration (young DBA/2), aging retina (aged C57) and aging retina challenged by elevated IOP (aged DBA/2). We found that: 1) neurodegenerative stressors induce alterations in whole retina expression of IL-6 and IL-6Rα, 2) these whole retina changes do not reflect the immediate milieu of RGCs, where IL-6 and IL-6Rα expression is spatially variable and 3) the extent and magnitude of this spatial variability is stressor-dependent. Our data provide the first evidence that neurodegenerative stressors produce microenvironments of IL-6 signaling in retina and that the nature and magnitude of spatial regulation is dependent on the identity of the stressor.
神经炎症被定义为中枢神经系统内免疫相关过程的诱导，被认为是许多神经退行性疾病的一个组成部分，包括视网膜神经节细胞（RGC）的青光眼性退变。先前的体外研究确定白细胞介素-6（IL-6）是RGC的一种潜在神经保护因子，尤其是那些受到青光眼相关应激源挑战的RGC。在这里，我们研究了IL-6信号在响应与RGC神经退行性变相关的两种应激源（年龄和眼压升高）时的时空特征。我们使用酶联免疫吸附测定（ELISA）、免疫印迹、免疫标记和定量显微镜技术，测量并比较了正常视网膜（年轻C57）、易发生青光眼性神经退行性变的视网膜（年轻DBA/2）、衰老视网膜（老年C57）以及受到眼压升高挑战的衰老视网膜（老年DBA/2）中整个视网膜和RGC相关的IL-6和IL-6Rα的表达。我们发现：1）神经退行性应激源会诱导整个视网膜中IL-6和IL-6Rα表达的改变；2）这些整个视网膜的变化并不能反映RGC的直接微环境，其中IL-6和IL-6Rα的表达在空间上是可变的；3）这种空间变异性的程度和大小取决于应激源。我们的数据首次证明，神经退行性应激源会在视网膜中产生IL-6信号的微环境，并且空间调节的性质和程度取决于应激源的特性。
