BACKGROUND Neural cell adhesion molecule (NCAM) belongs to the immunoglobulin superfamily of adhesion molecules. Polysialic acid (PSA) is attached to NCAM post-translationally. PSA residues are considered to reduce the adhesive properties of NCAM and play an important role in the regulation of cell interactions. PSA-NCAM is largely expressed in the mature retina by glial cells adjacent to retinal ganglion cells (RGCs) but its functions remain unclear. The objective of this study was to explore the role of PSA-NCAM with respect to RGC survival following kainic acid (KA)-induced excitotoxicity. METHODS Experiments were performed on C57BL/6NTac male mice. KA was injected intravitreally to induce RGC damage. RGCs were visualized using an anti-Brn3a antibody. Endoneuraminidase N (NA) was administrated intravitreally to cleave PSA chains from NCAM. RESULTS KA induced an 80% reduction in the density of RGCs that was accompanied by a decrease in PSA-NCAM in the RGC layer. KA treatment induced a pronounced increase in the level of matrix metalloproteinase-9 (MMP-9) in the inner layers of the retina. Inhibition of MMP-9 reduced both RGC death and PSA-NCAM shedding in the retina. PSA-NCAM cleavage induced by NA abolished the protective action of the MMP-9 inhibitor and decreased RGC survival following KA-treatment. CONCLUSIONS A decrease in retinal PSA-NCAM levels following KA administration is due to the induction of active MMP-9, which removes extracellular PSA-NCAM from the surface of astroglial and Müller cells. The MMP-9 induced shedding of PSA-NCAM enhances KA-induced toxicity and at least in part contributes to the observed loss of RGCs following excitotoxic damage.

中文翻译：

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海藻酸损害后，PSA-NCAM在视网膜神经节细胞（RGC）存活中的作用。

背景技术神经细胞粘附分子（NCAM）属于粘附分子的免疫球蛋白超家族。聚唾液酸（PSA）在翻译后与NCAM相连。PSA残基被认为会降低NCAM的粘合性能，并在调节细胞相互作用中起重要作用。PSA-NCAM主要由邻近视网膜神经节细胞（RGC）的神经胶质细胞在成熟视网膜中表达，但其功能尚不清楚。这项研究的目的是探讨PSA-NCAM在海藻酸（KA）引起的兴奋性毒性后相对于RGC存活的作用。方法对C57BL / 6NTac雄性小鼠进行实验。玻璃体内注射KA引起RGC损伤。使用抗Brn3a抗体将RGC可视化。玻璃体内施用神经内酰胺酶N（NA）以从NCAM切割PSA链。结果KA诱导RGC密度降低80％，同时RGC层中PSA-NCAM降低。KA处理在视网膜内层引起基质金属蛋白酶9（MMP-9）的水平显着增加。抑制MMP-9可减少RGC死亡和视网膜PSA-NCAM脱落。NA诱导的PSA-NCAM裂解消除了MMP-9抑制剂的保护作用，并降低了KA处理后的RGC存活率。结论KA给药后视网膜PSA-NCAM水平降低归因于活性MMP-9的诱导，该活性从星形胶质细胞和Müller细胞表面去除了细胞外PSA-NCAM。MMP-9诱导的PSA-NCAM的脱落增强了KA诱导的毒性，并且至少部分参与了兴奋性毒性损伤后观察到的RGC的损失。