Vaccination for neuroprotection in the mouse optic nerve: Implications for optic neuropathies

Vaccination for neuroprotection in the mouse optic nerve: Implications for optic neuropathies
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DOI:
10.1523/jneurosci.21-01-00136.2001
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发表时间:
2001-01-01
影响因子:
5.3
通讯作者:
Schwartz, M
Schwartz, M
中科院分区:
医学1区
文献类型:
--
作者:
Fisher, J;Levkovitch-Verbin, H;Schwartz, M

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T细胞自身免疫髓鞘碱性蛋白最近被证明是神经保护损伤的大鼠视神经。在本研究中,使用小鼠视神经,我们研究了主动免疫而不是被动转移T细胞是否有利于保护视网膜神经节细胞(RGC)免受创伤后死亡。视神经严重挤压伤前,SJL/J和C3 H。SW小鼠主动免疫致脑炎或非致脑炎的蛋白脂质蛋白(PLP)或髓鞘少突胶质细胞糖蛋白(MOG)的肽,分别。在损伤后的不同时间,用非致脑炎肽pPLP 190-209或pMOG 1-22免疫的两种菌株中存活的RGC的数量显著高于用非自身抗原卵清蛋白或用衍生自β-淀粉样蛋白(一种非髓鞘相关蛋白)的肽处理的损伤对照。用致脑炎髓鞘肽pPLP 139-151免疫仅在其诱导的疾病(实验性自身免疫性脑脊髓炎)为轻度时有益。这项研究的结果表明,轴突损伤后的RGCs的存活率可以通过接种适当的自身抗原来提高。此外,使用非致脑炎性髓鞘肽进行免疫接种显然允许神经保护而不引起自身免疫性疾病的风险。这些发现的应用可能会导致一个有前途的新方法来治疗视神经病变,如青光眼。
T-cell autoimmunity to myelin basic protein was recently shown to be neuroprotective in injured rat optic nerves. In the present study, using the mouse optic nerve, we examined whether active immunization rather than passive transfer of T-cells can be beneficial in protecting retinal ganglion cells (RGCs) from post-traumatic death. Before severe crush injury of the optic nerve, SJL/J and C3H. SW mice were actively immunized with encephalitogenic or nonencephalitogenic peptides of proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG), respectively. At different times after the injury, the numbers of surviving RGCs in both strains immunized with the nonencephalitogenic peptides pPLP 190-209 or pMOG 1-22 were significantly higher than in injured controls treated with the non-self-antigen ovalbumin or with a peptide derived from beta -amyloid, a non-myelin-associated protein. Immunization with the encephalitogenic myelin peptide pPLP 139-151 was beneficial only when the disease it induced, experimental autoimmune encephalomyelitis, was mild. The results of this study show that survival of RGCs after axonal injury can be enhanced by vaccination with an appropriate self-antigen. Furthermore, the use of nonencephalitogenic myelin peptides for immunization apparently allows neuroprotection without incurring the risk of an autoimmune disease. Application of these findings might lead to a promising new approach for treating optic neuropathies such as glaucoma.