视网膜下小胶质细胞支持 rd1 小鼠供体光感受器的存活。

Subretinal microglia support donor photoreceptor survival in rd1 mice.

机构信息

Department of Ophthalmology, West China Hospital, Sichuan University, Cheng Du, Sichuan, China.

出版信息

Stem Cell Res Ther. 2024 Nov 19;15(1):436. doi: 10.1186/s13287-024-04052-0.

PURPOSE

To investigate the potential relationship between subretinal microglia and transplanted donor photoreceptors.

METHODS

Photoreceptor precursors were transplanted into wild-type mice and rd1 mice by trans-scleral injection. Immunohistochemistry was employed to detect microglia and macrophages. PlX5622 feed was used to achieve microglia depletion and microglia repopulation. RNA-seq and qPCR were utilized to evaluate gene expression. Confocal microscopy was used to observe the interaction between microglia and donor photoreceptors.

RESULTS

Donor photoreceptors survived in rd1 mice but not in wild-type mice after trans-scleral injection. The microglial cells closely interacted with donor cells. While donor cells failed to survive in rd1 mice after microglia depletion, they could survive following microglia repopulation. The RNA-seq analysis showed a pro-neurodevelopmental effect of sub-retinal microglia/RPE tissue in rd1 mice.

CONCLUSIONS

Subretinal microglia supported donor photoreceptor survival in rd1 mice.

目的

研究视网膜下微胶质细胞与移植供体光感受器之间的潜在关系。

方法

通过巩膜内注射将光感受器前体细胞移植到野生型小鼠和 rd1 小鼠中。采用免疫组织化学方法检测小胶质细胞和巨噬细胞。利用 PlX5622 饲料实现小胶质细胞耗竭和小胶质细胞再群体化。采用 RNA-seq 和 qPCR 评估基因表达。利用共聚焦显微镜观察小胶质细胞与供体光感受器之间的相互作用。

结果

供体光感受器在 rd1 小鼠中经巩膜内注射后存活，但在野生型小鼠中未存活。小胶质细胞与供体细胞密切相互作用。虽然在 rd1 小鼠中小胶质细胞耗竭后供体细胞无法存活，但在小胶质细胞再群体化后它们可以存活。RNA-seq 分析显示，视网膜下小胶质细胞/RPE 组织在 rd1 小鼠中具有促进神经发育的作用。