Protection of the Retinal Ganglion Cells: Intravitreal Injection of Resveratrol in Mouse Model of Ocular Hypertension

Invest Ophthalmol Vis Sci. 2020 Mar 9;61(3):13. doi: 10.1167/iovs.61.3.13.

Abstract

Purpose: To investigate the efficacy of intravitreal administration of resveratrol (RSV) in a microbead-induced high intraocular pressure (IOP) murine model for glaucoma.

Methods: Experiments were performed using adult C57BL/6JJcl mice. Polystyrene microbeads were injected into the anterior chamber to induce IOP elevation. Retinal flat-mounts and sections were assessed by immunohistochemistry to detect the expression of reactive oxygen species and acetyl-p53 in retinal ganglion cells (RGCs), brain-derived neurotrophic factor (BDNF) in Müller glial cells (MGCs), and the receptor tropomyosin receptor kinase B (TrkB) in RGCs. Light cycler real-time PCR was also used for confirming gene expression of BDNF in primary cultured MGCs exposed to RSV.

Results: Microbeads induced high IOP followed by RGC death and axon loss. Administration of RSV rescued RGCs via decreased reactive oxygen species generation and acetyl-p53 expression in RGCs and upregulated BDNF in MGCs and TrkB expression in RGCs, which exhibited a strong cytoprotective action against cell death through multiple pathways under high IOP.

Conclusions: Our data suggest that administration of RSV may delay the progress of visual dysfunction during glaucoma and may therefore have therapeutic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Death / drug effects
  • Cells, Cultured
  • Cytoprotection / physiology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Intraocular Pressure / drug effects
  • Intravitreal Injections
  • Male
  • Mice, Inbred C57BL
  • Microspheres
  • Ocular Hypertension / drug therapy*
  • Ocular Hypertension / etiology
  • Ocular Hypertension / metabolism
  • Ocular Hypertension / pathology
  • Reactive Oxygen Species / metabolism
  • Resveratrol / administration & dosage
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use*
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Sirtuin 1 / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antioxidants
  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Resveratrol