Subretinal microglia support donor photoreceptor survival in rd1 mice

Abstract

Abstract 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.

Keywords

• Subretinal microglia
• Photoreceptor transplantation
• Inherited retinal degeneration