PDF(Pubmed)
Abstract：
As photoreceptor cells die during retinal degeneration, the surrounding microenvironment undergoes significant changes that are increasingly recognized to play a prominent role in determining the efficacy of therapeutic interventions. Chondroitin Sulphate Proteoglycans (CSPGs) are a major component of the extracellular matrix that have been shown to inhibit neuronal regrowth and regeneration in the brain and spinal cord, but comparatively little is known about their expression in retinal degeneration. Here we provide a comprehensive atlas of the expression patterns of four individual CSPGs in three models of inherited retinal degeneration and wildtype mice. In wildtype mice, Aggrecan presented a biphasic expression, while Neurocan and Phosphacan expression declined dramatically with time and Versican expression remained broadly constant. In degeneration, Aggrecan expression increased markedly in Aipl1-/- and Pde6brd1/rd1, while Versican showed regional increases in the periphery of Rho-/- mice. Conversely, Neurocan and Phosphacan broadly decrease with time in all models. Our data reveal significant heterogeneity in the expression of individual CSPGs. Moreover, there are striking differences in the expression patterns of specific CSPGs in the diseased retina, compared with those reported following injury elsewhere in the CNS. Better understanding of the distinct distributions of individual CSPGs will contribute to creating more permissive microenvironments for neuro-regeneration and repair.
摘要：
当感光细胞在视网膜变性时死亡,周围的微环境发生了显著的变化,人们越来越认识到这些变化在决定治疗干预措施的疗效方面发挥着重要作用.硫酸软骨素蛋白聚糖（CSPGs）是细胞外基质的主要成分，已被证明可以抑制大脑和脊髓中的神经元再生和再生。但是对它们在视网膜变性中的表达知之甚少。在这里，我们提供了三个遗传性视网膜变性和野生型小鼠模型中四个单独CSPGs表达模式的综合图集。在野生型小鼠中,Aggrecan呈现双相表达，而Neurocan和phophacan的表达随时间急剧下降，Versican的表达保持大致恒定。在退化中，Aggrecan在Aipl-/-和Pde6brd1/rd1中的表达显着增加，而Versican在Ro-/-小鼠的外周显示出区域增加。相反，在所有模型中，Neurocan和磷酸an随时间广泛减少。我们的数据揭示了单个CSPGs表达的显著异质性。此外，在病变的视网膜中，特定CSPGs的表达模式存在显著差异，与中枢神经系统其他部位受伤后报告的相比。更好地了解各个CSPG的不同分布将有助于为神经再生和修复创造更多的微环境。
