Neuroprotective Effect of Curcumin Against Oxidative Damage in BV-2 Microglia and High Intraocular Pressure Animal Model

J Ocul Pharmacol Ther. 2014 Oct;30(8):657-64. doi: 10.1089/jop.2014.0022. Epub 2014 Jun 25.

Abstract

Purpose: The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. In this study, we aim to evaluate the antioxidant effects of curcumin in BV-2 microglia oxidative damage and assess its neuroprotective effects in a chronic high IOP rat model.

Methods: BV-2 microglia cell line was used in an in vitro study and Wistar rats were used in an in vivo study. Cultured BV-2 microglia cells were pretreated with 10, 1, or 0.1 μM curcumin for 1 h, and sustained oxidative stress was induced by subjecting BV-2 microglia to 200 μM hydrogen peroxide (H2O2) for 24 h. MTT assay was used to determine cell viability. Changes of intracellular reactive oxygen species (ROS) and apoptosis were analyzed by flow cytometry. Three episcleral veins were cauterized to induce high IOP in Wistar rats and measured by Tonopen. After 6 weeks of treatment with curcumin (10 mg/kg/day) by intragastric administration, surviving of retinal ganglion cells was quantified. Activation of caspase 3, cytochrome c, BAX, and BCL2 was quantified by Western blotting both in BV-2 microglia and in animal model. Data were analyzed with the GraphPad Prism 5.0 software, and P<0.05 was considered to be statistically significant.

Results: The in vitro study showed that when BV-2 microglia was pretreated with curcumin, the cell viability increased and the intracellular ROS and apoptosis significantly decreased. In the in vivo study, chronic mild IOP elevation was induced for 4 weeks. In the curcumin-treated group, curcumin protected rat BV-2 microglia from death significantly. In both H2O2-treated BV-2 microglia and glaucoma models, caspase 3, cytochrome c, and BAX were downregulated and BCL2 was upregulated in the curcumin-treated group.

Conclusions: Curcumin affords neuroprotective effects by inhibiting oxidative damage and could be a new or adjunctive treatment for glaucoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Curcumin / administration & dosage
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry
  • Humans
  • Intraocular Pressure / drug effects*
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Ocular Hypertension / drug therapy*
  • Ocular Hypertension / metabolism
  • Oxidative Stress / drug effects*
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism

Substances

  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Curcumin