Endogenous tissue type plasminogen activator facilitates NMDA-induced retinal damage.

Abstract

To investigate the role of tissue plasminogen activator (tPA) in retinal damage, tPA-deficient and wild-type mice were employed. Two different retinal neuron insult models were used in the present study. One is an excitotoxin-treated retinal model, created by direct intravitreal injection of glutamate analogs, NMDA or kainic acid (KA), and the other is an ischemia-reperfusion model induced by transient elevation of intraocular pressure. TdT-dUTP terminal nick-end labeling (TUNEL) method was used to examine the retinal cell nuclear damage. The number of TUNEL-positive cells in ganglion cell layer (GCL) and inner nuclear layer (INL) in tPA-deficient mice after low-, but not high-dose NMDA was significantly less compared to wild type. In contrast, neither intravitreal KA or transient ischemia produced significant difference in retinal damage in tPA vs. wild-type mice. These data show that tPA-deficient mice are resistant to retinal damage by intravitreal injection of NMDA, and indicate that tPA plays a role in the retinal cell damage induced by excitotoxins, especially NMDA.

• Authors: Masako Kumada, Masayuki Niwa, Xiaodan Wang, Hiroyuki Matsuno, Akira Hara, Hideki Mori, Osamu Matsuo, Tetsuya Yamamoto, Osamu Kozawa
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 200 Issue 1 Pg. 48-53 (Oct 01 2004) ISSN: 0041-008X [Print] United States
• PMID: 15451307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Agonists
• Glutamates
• Plasminogen Inactivators
• Recombinant Proteins
• N-Methylaspartate
• Kainic Acid

Topics

• Animals
• Cell Count
• DNA Fragmentation
• Excitatory Amino Acid Agonists (administration & dosage, pharmacology)
• Glutamates (administration & dosage, pharmacology)
• In Situ Nick-End Labeling
• Injections
• Kainic Acid (administration & dosage, pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• N-Methylaspartate (administration & dosage, toxicity)
• Neurons (drug effects)
• Plasminogen Inactivators (deficiency, physiology)
• Recombinant Proteins (pharmacology)
• Reperfusion Injury (pathology, prevention & control)
• Retina
• Retinal Diseases (chemically induced, pathology)
• Retinal Ganglion Cells (drug effects)