Explore the molecular mechanism of angle-closure glaucoma in elderly patients induced telomere shortening of retinal ganglion cells through oxidative stress

Nucleosides Nucleotides Nucleic Acids. 2022;41(10):1024-1035. doi: 10.1080/15257770.2022.2094947. Epub 2022 Jul 8.

Abstract

Senile glaucoma is a common ophthalmological disease in the elderly. It is a disease of visual papillary perfusion caused by elevated intraocular pressure, complicated by visual dysfunction. Glaucoma can cause serious damage to the normal vision of the elderly. Therefore, exploring the related molecular mechanisms of glaucoma is of great significance to the diagnosis and treatment of glaucoma. This is an exploratory study. Establish a mouse model and conduct experimental groupings. After one week of adaptive feeding, the mice were intraperitoneally injected with an anesthetic mixture: ketamine + xylazine. Then the mice were sacrificed by neck dissection, and the eyeball tissues were immediately dissected. HE staining was used to analyze the histopathological characteristics of the retina of each group of mice. MitoSOX fluorescent probe was used to analyze the content of ROS in retinal tissue. The ELISA analysis was used to detect the activation of β-galactosidase for the aging characteristics of retinal ganglion cells in retinal tissues. Immunohistochemistry experiments were used to analyze the expression of telomerase TERT in retinal tissues. Western blot analysis was used to determine the expression of proteins POT1, TERF1, TERF2, and TINF2 in retinal tissues. The HE staining experiment showed that the damage of retinal tissue decreased from group Glaucoma to group Old, group Old to group Young. The experimental results of MitoSOX fluorescent probe show that ROS content is positively correlated with the degree of tissue damage. ELISA analysis results showed that the expression trend of β-galactosidase was the same as the ROS content. The protein expression levels related to telomere protection (TRET, POT1, TREF1, TREF2 and TINF2) all increased from group Glaucoma to group Old, group Old to group Young. The increase in ROS content, the decrease in telomere protection-related protein expression (telomere shortening) induced by ROS, and the increase of the expression of β-galactosidase, are all potential molecular mechanisms for the occurrence of angle-closure glaucoma in elderly patients.

Keywords: C-nucleosides; Femoral shaft fractdure (FSF); antibacterial nucleosides; autotransfusion; hemodilution; predeposit; salvage.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fluorescent Dyes / metabolism
  • Glaucoma* / metabolism
  • Glaucoma* / pathology
  • Glaucoma, Angle-Closure* / metabolism
  • Glaucoma, Angle-Closure* / pathology
  • Intraocular Pressure
  • Ketamine* / metabolism
  • Mice
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Telomerase*
  • Telomere Shortening
  • Xylazine / metabolism
  • beta-Galactosidase / metabolism

Substances

  • Fluorescent Dyes
  • Reactive Oxygen Species
  • Xylazine
  • Ketamine
  • Telomerase
  • beta-Galactosidase