Neuroprotective effect of epigallocatechin-3-gallate against N-methyl-D-aspartate-induced excitotoxicity in the adult rat retina

Acta Ophthalmol. 2012 Dec;90(8):e609-15. doi: 10.1111/j.1755-3768.2012.02502.x. Epub 2012 Sep 13.

Abstract

Purpose: Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has been suggested to reduce glutamate excitotoxicity. We therefore investigated the potentially protective effects of EGCG against N-methyl-d-aspartate (NMDA)-induced excitotoxicity in the retina.

Methods: Female Wistar rats (n = 171) were divided into a normal control group (n = 9); saline control group with intravitreal saline injections (n = 54); NMDA control group with an intravitreal NMDA injection and intraperitoneal saline injections (n = 54); and NMDA study group (n = 54) receiving an intravitreal NMDA injection plus intraperitoneal EGCG (25 mg/kg) injections. Starting at 2 days prior to the intravitreal NMDA injection, the intraperitoneal injections were performed daily for the whole study period. At 12 hr, 1, 2, 3 days, 1 and 2 weeks after the intravitreal NMDA injection, the animals were killed. We counted the neurons in the retinal ganglion cell layer (GCL) on histological sections, measured the thickness of Thy-1 immunoreactivity and assessed the expression of Thy-1 mRNA by real-time polymerase chain reaction.

Results: At all time-points, GCL cell density, thickness of Thy-1 immunoreactivity and expression of Thy-1 mRNA were significantly (all p < 0.05) lower in the NMDA control group than in the NMDA study group, in which the parameters were significantly (all p < 0.05) lower than in the saline control group and the normal control group. In both groups with an intravitreal NMDA injection, GCL cell density, thickness of Thy-1 immunoreactivity and expression of Thy-1 mRNA decreased significantly with increasing follow-up time.

Conclusions: Intraperitoneal application of EGCG resulted in a significantly less marked NMDA-associated loss of retinal ganglion cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Count
  • Cell Survival / drug effects
  • Excitatory Amino Acid Agonists / toxicity*
  • Female
  • Injections, Intraperitoneal
  • N-Methylaspartate / toxicity*
  • Neuroprotective Agents / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Retinal Degeneration / chemically induced
  • Retinal Degeneration / genetics
  • Retinal Degeneration / pathology
  • Retinal Degeneration / prevention & control*
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Thy-1 Antigens / genetics
  • Thy-1 Antigens / metabolism

Substances

  • Excitatory Amino Acid Agonists
  • Neuroprotective Agents
  • RNA, Messenger
  • Thy-1 Antigens
  • N-Methylaspartate
  • Catechin
  • epigallocatechin gallate