Increased inflammation in older high-pressure glaucoma mice

Neurobiol Aging. 2025 Jan:145:55-64. doi: 10.1016/j.neurobiolaging.2024.10.001. Epub 2024 Oct 9.

Abstract

Besides an elevated intraocular pressure (IOP), advanced age is one of the most crucial risk factors for developing glaucoma. βB1-Connective Tissue Growth Factor (βB1-CTGF) high-pressure glaucoma mice were used in this study to assess whether glaucoma mice display more inflammatory and aging processes than age-matched controls. Therefore, 20-month-old βB1-CTGF and corresponding wildtype (WT) controls were examined. After IOP measurements, retinas were processed for (immuno-)histological and quantitative real-time PCR analyses. A significantly higher IOP and diminished retinal ganglion cell numbers were noted in βB1-CTGF mice compared to WT. An enhanced macrogliosis as well as an increased number of microglia/macrophages and microglia was detected in retinas of old glaucoma mice. Interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and transforming growth factor-β2 were upregulated, suggesting an ongoing inflammation. Moreover, βB1-CTGF retinas displayed an increased senescence-associated β-galactosidase staining accompanied by a downregulation of Lmnb1 (laminin-B1) mRNA levels. Our results provide a deeper insight into the association between inflammation and high-pressure glaucoma and thus might help to develop new therapy strategies.

Keywords: Aging; Glaucoma; High-pressure; Inflammation; Interleukins; Senescence.

MeSH terms

  • Aging* / genetics
  • Aging* / pathology
  • Animals
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Disease Models, Animal
  • Glaucoma* / etiology
  • Glaucoma* / genetics
  • Glaucoma* / pathology
  • Inflammation* / genetics
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Intraocular Pressure* / physiology
  • Macrophages / metabolism
  • Mice
  • Microglia* / metabolism
  • Microglia* / pathology
  • Retina* / metabolism
  • Retina* / pathology
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation

Substances

  • Connective Tissue Growth Factor
  • Transforming Growth Factor beta1
  • Interleukin-1beta