Sex and Age-Related Differences in Neuroinflammation and Apoptosis in Balb/c Mice Retina Involve Resolvin D1

Int J Mol Sci. 2021 Jun 11;22(12):6280. doi: 10.3390/ijms22126280.

Abstract

(1) Background: The pro-resolving lipid mediator Resolvin D1 (RvD1) has already shown protective effects in animal models of diabetic retinopathy. This study aimed to investigate the retinal levels of RvD1 in aged (24 months) and younger (3 months) Balb/c mice, along with the activation of macro- and microglia, apoptosis, and neuroinflammation. (2) Methods: Retinas from male and female mice were used for immunohistochemistry, immunofluorescence, transmission electron microscopy, Western blotting, and enzyme-linked immunosorbent assays. (3) Results: Endogenous retinal levels of RvD1 were reduced in aged mice. While RvD1 levels were similar in younger males and females, they were markedly decreased in aged males but less reduced in aged females. Both aged males and females showed a significant increase in retinal microglia activation compared to younger mice, with a more marked reactivity in aged males than in aged females. The same trend was shown by astrocyte activation, neuroinflammation, apoptosis, and nitrosative stress, in line with the microglia and Müller cell hypertrophy evidenced in aged retinas by electron microscopy. (4) Conclusions: Aged mice had sex-related differences in neuroinflammation and apoptosis and low retinal levels of endogenous RvD1.

Keywords: aging; apoptosis; neuroprotection; retina.

MeSH terms

  • Aging / pathology*
  • Animals
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Caspase 3 / metabolism
  • Docosahexaenoic Acids / pharmacology*
  • Ependymoglial Cells / drug effects
  • Ependymoglial Cells / metabolism
  • Ependymoglial Cells / pathology
  • Ependymoglial Cells / ultrastructure
  • Female
  • Inflammation / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology
  • Microglia / ultrastructure
  • NF-kappa B / metabolism
  • Retina / drug effects
  • Retina / pathology*
  • Sex Characteristics*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Biomarkers
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • resolvin D1
  • Docosahexaenoic Acids
  • 3-nitrotyrosine
  • Tyrosine
  • Caspase 3