Endogenous tissue type plasminogen activator facilitates NMDA-induced retinal damage
Autor: | Masayuki Niwa, Tetsuya Yamamoto, Hideki Mori, Xiaodan Wang, Masako Kumada, Akira Hara, Hiroyuki Matsuno, Osamu Kozawa, Osamu Matsuo |
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Rok vydání: | 2004 |
Předmět: |
Retinal Ganglion Cells
Kainic acid N-Methylaspartate Cell Count DNA Fragmentation Biology Toxicology Retina Injections Mice chemistry.chemical_compound Glutamates Retinal Diseases Excitatory Amino Acid Agonists In Situ Nick-End Labeling medicine Animals Ganglion cell layer Mice Knockout Neurons Pharmacology Kainic Acid T-plasminogen activator Retinal Recombinant Proteins Cell biology Mice Inbred C57BL Plasminogen Inactivators medicine.anatomical_structure chemistry Biochemistry Reperfusion Injury Inner nuclear layer NMDA receptor Plasminogen activator |
Zdroj: | Toxicology and Applied Pharmacology. 200:48-53 |
ISSN: | 0041-008X |
DOI: | 10.1016/j.taap.2004.03.017 |
Popis: | 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. |
Databáze: | OpenAIRE |
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