Protective effect of all-trans retinoic acid on NMDA-induced neuronal cell death in rat retina.

Abstract

We histologically examined the effects of all-trans retinoic acid (ATRA) on neuronal injury induced by intravitreous injection of N-methyl-d-aspartic acid (NMDA) (200nmol/eye). Treatment with ATRA for 7 days (15mg/kg for the first two days and 10mg/kg for the following five days, p.o.) reduced the decrease of cell number in the ganglion cell layer and the inner nuclear layer 7 days after NMDA injection. TUNEL staining 6h after NMDA injection showed that treatment with ATRA (15mg/kg, p.o.) 1h prior to NMDA injection reduced the number of apoptotic cells in the ganglion cell layer and inner nuclear layer. The anti-apoptotic effect of ATRA was vanished by intravitreous injection of U0126, an extracellular signal-regulated kinase/mitogen-activated protein kinase kinase inhibitor (1nmol/eye). These results suggest that ATRA has a protective effect, which is medicated by extracellular signal-regulated kinase pathway, on NMDA-induced apoptosis in the rat retina. ATRA may be useful as a therapeutic drug against retinal diseases that cause glutamate neurotoxicity.

• Authors: Kenji Sakamoto, Masahide Hiraiwa, Maki Saito, Tsutomu Nakahara, Yoji Sato, Taku Nagao, Kunio Ishii
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 635 Issue 1-3 Pg. 56-61 (Jun 10 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20303946 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butadienes
• Nitriles
• Protein Kinase Inhibitors
• U 0126
• Tretinoin
• N-Methylaspartate
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Butadienes (pharmacology)
• Dose-Response Relationship, Drug
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors)
• Injections
• Male
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors)
• N-Methylaspartate (administration & dosage, pharmacology)
• Neurons (drug effects, pathology)
• Nitriles (pharmacology)
• Protein Kinase Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Retina (drug effects, injuries, pathology)
• Tretinoin (pharmacology)