Rescuing cones and daylight vision in retinitis pigmentosa mice

FASEB J. 2019 Sep;33(9):10177-10192. doi: 10.1096/fj.201900414R. Epub 2019 Jun 14.

Abstract

Hallmark of retinitis pigmentosa (RP) is the primary, genetic degeneration of rods followed by secondary loss of cones, caused by still elusive biologic mechanisms. We previously shown that exposure of rd10 mutant mice, modeling autosomal recessive RP, to environmental enrichment (EE), with enhanced motor, sensorial and social stimuli, results into a sensible delay of retinal degeneration and vision loss. Searching for effectors of EE-mediated retinal protection, we performed transcriptome analysis of the retina of rd10 enriched and control mice and found that gene expression at the peaks of rod and cone degeneration is characterized by a strong inflammatory/immune response, which is however measurably lower in enrichment conditions. Treating rd10 mice with dexamethasone during the period of maximum photoreceptors death lowered retinal inflammation and caused a preservation of cones and cone-mediated vision. Our findings indicate a link between retinal inflammation and bystander cone degeneration, reinforcing the notion that cone vision in RP can be preserved using anti-inflammatory approaches.-Guadagni, V., Biagioni, M., Novelli, E., Aretini, P., Mazzanti, C. M., Strettoi, E. Rescuing cones and daylight vision in retinitis pigmentosa mice.

Keywords: bystander effect; cytokines; environmental enrichment; microglia; rod.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Survival
  • Color Vision / physiology*
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / deficiency
  • Dexamethasone / therapeutic use*
  • Disease Progression
  • Drug Evaluation, Preclinical
  • Female
  • Gene Expression Regulation
  • Macrophage Activation
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Retinal Cone Photoreceptor Cells / pathology
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Rod Photoreceptor Cells / enzymology
  • Retinal Rod Photoreceptor Cells / pathology
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology
  • Transcriptome
  • Visual Acuity

Substances

  • Anti-Inflammatory Agents
  • Dexamethasone
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Pde6b protein, mouse