Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment

Cell Death Dis. 2021 Oct 9;12(10):926. doi: 10.1038/s41419-021-03983-3.

Abstract

Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Calcium-Binding Proteins / metabolism
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Line
  • Disease Models, Animal
  • Gene Expression Profiling
  • Light
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Knockout
  • Microfilament Proteins / metabolism
  • Microglia / drug effects
  • Microglia / metabolism*
  • Microglia / pathology*
  • Models, Biological
  • Myosin Type I / metabolism*
  • Myosins / metabolism*
  • Photoreceptor Cells, Vertebrate / drug effects
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Photoreceptor Cells, Vertebrate / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrroles / pharmacology
  • Retinal Degeneration / genetics
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology
  • Retinal Detachment / genetics
  • Retinal Detachment / metabolism*
  • Retinal Detachment / pathology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Aif1 protein, mouse
  • Aminopyridines
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Myo1f protein, mouse
  • Pyrroles
  • pexidartinib
  • Proto-Oncogene Proteins c-akt
  • Myosin Type I
  • Myosins