A comprehensive atlas of Aggrecan, Versican, Neurocan and Phosphacan expression across time in wildtype retina and in retinal degeneration.

A comprehensive atlas of Aggrecan, Versican, Neurocan and Phosphacan expression across time in wildtype retina and in retinal degeneration.
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野生型视网膜和视网膜变性中聚集蛋白聚糖、Versican、Neurocan和Phosphacan随时间表达的综合图谱。

DOI:
10.1038/s41598-022-11204-w
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发表时间:
2022-05-04
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
文献类型:
--
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随着视网膜变性过程中感光细胞的死亡,周围的微环境发生了显著的变化,这些变化越来越多地被认为在决定治疗干预的疗效方面发挥了重要作用。硫酸软骨素蛋白聚糖(CSPG)是细胞外基质的主要成分,其已显示出抑制脑和脊髓中的神经元再生和再生,但关于其在视网膜变性中的表达相对知之甚少。在这里,我们提供了一个全面的图集的表达模式的四个单独的CSPGs在三个模型的遗传性视网膜变性和野生型小鼠。在野生型小鼠中,聚集蛋白聚糖呈现双相表达,而Neurocan和Phosphacan表达随时间显著下降,Versican表达保持大致恒定。在变性中,聚集蛋白聚糖表达在Aipl 1-/-和Pde 6 brd 1/rd 1中显著增加,而Versican在Rho-/-小鼠的外周中显示区域性增加。相反,在所有模型中,Neurocan和Phosphacan随时间广泛降低。我们的数据揭示了个体CSPGs表达的显著异质性。此外,有显着的差异,在特定的CSPGs在患病的视网膜的表达模式,与那些报道的损伤后,在中枢神经系统的其他地方。更好地了解个体CSPG的不同分布将有助于为神经再生和修复创造更宽松的微环境。
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.
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