Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light

Cell Death Dis. 2016 Nov 10;7(11):e2468. doi: 10.1038/cddis.2016.363.

Abstract

Age-related macular degeneration (AMD), the leading cause of visual loss after the age of 60 years, is a degenerative retinal disease involving a variety of environmental and hereditary factors. Although it has been implicated that immune system is involved in the disease progression, the exact role that microglia has is still unclear. Here we demonstrated that knockout of Ccr2 gene could alleviate photoreceptor cell death in mice retinas exposed to chronic blue light. In Ccr2-/- mice, a damaged microglia recruitment was shown in retina and this could protect the visual function in electroretinogram and alleviate the photoreceptor apoptosis, which thus helped attenuate the blue light-induced retinopathy. We further found an increased co-location of NLRP3, Iba-1, and IL-1β in fluorescence and a concomitant increased protein expression of NLRP3, caspase-1, and IL-1β in western blotting in chronic blue light-induced retinopathy. Moreover, the activation of microglia and their cellular NLRP3 inflammasomes occurred as an earlier step before the structural and functional damage of the mice retinas, which collectively supported that microglial NLRP3 inflammasome might be the key to the chronic blue light-induced retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Caspase 1 / metabolism
  • Cell Death / radiation effects
  • Electroretinography
  • Fluorescent Antibody Technique
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • Light*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / metabolism
  • Microglia / pathology
  • Microglia / radiation effects
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Photoreceptor Cells / metabolism*
  • Photoreceptor Cells / pathology*
  • Receptors, CCR2 / deficiency*
  • Receptors, CCR2 / metabolism
  • Retina / pathology*
  • Retina / physiopathology
  • Retina / radiation effects*
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Vision, Ocular / radiation effects

Substances

  • Ccr2 protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Receptors, CCR2
  • Caspase 1