间充质干细胞外泌体治疗小鼠视网膜色素变性的作用和机制研究

视网膜色素变性（RP）是一种不可逆转的致盲性眼科疾病，研究表明干细胞移植为治疗RP提供了新希望，但也面临如伦理、免疫排斥等问题。干细胞外泌体携带了干细胞有效成分、具有低免疫原性和便于给药等优势。我们预实验应用RP小鼠模型，发现间充质干细胞外泌体能够改善小鼠视觉功能、延缓视网膜感光细胞死亡、降低pro-IL-1β的表达、抑制胶质细胞的激活。鉴于此，我们提出：间充质干细胞外泌体能够改善RP小鼠视网膜局部微环境，延缓视网膜细胞退变，促进视觉功能的恢复。项目拟应用RP转基因小鼠模型，结合形态学、功能学、分子生物学等技术，分析外泌体对RP小鼠视网膜结构、功能和局部微环境的影响，探索外泌体中的如microRNA等有效作用成分。预期研究为RP的治疗新策略奠定理论基础。

Retinitis pigmentosa (RP) is an irreversible blinding eye disease. Studies have shown that stem cell transplantation provides new hope for the treatment of RP, but it still faces problems such as ethics and immune rejection. Stem cell derived exosomes which carry stem cell active components have the advantages of low immunogenicity and easy administration. In our preliminary experiments, using RP mouse model, the exosomes derived from mesenchymal stem cells can improve the visual function, delay the death of retinal photoreceptor cells, reduce the expression of pro-IL-1β and inhibit the activation of glial cells. In view of this, we propose that: mesenchymal stem cell derived exosomes can improve the local retinal microenvironment of RP mice, delay the degeneration of retinal cells, and promote the recovery of visual function. The project intends to analyze the effects of exosomes on the retinal structure, function and local microenvironment of RP mice by using RP transgenic mouse model combined with morphological, functional and molecular biology techniques, and explore the effective components such as microRNA in exosomes. It is expected that the research will lay a theoretical foundation for the new treatment strategy of RP.