Retinal toxicity of commercial tissue plasminogen activator is mediated by the induction of nitric oxide in the mouse retinal primary cells

Hyun Sub Oh, Oh W. Kwon, In Chung, Sungchul Lee, Hyoung J. Koh, Sung Ho Lee, Joon H. Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: Tissue plasminogen activator (tPA) is an efficient thrombolytic agent, but the dose-dependent retinal toxicity of intravitreal injection of commercial tPA (containing L-arginine) has been reported. Here, we sought to investigate the mechanism of tPA-induced cell death in mouse retinal cell cultures and the role of nitric oxide (NO). Methods: Primary retinal cell cultures were maintained using glial conditioned medium (GCM) solution. Mouse retinal cell death was observed by using Hoechst-propidium iodide staining. Mouse retinal cell death was also measured by lactate dehydrogenase (LDH) assay. The formation of NO was measured using Griess reagent. Results: tPA-induced cell death was detected in mouse retinal cell cultures by Hoechst-propidium iodide staining or LDH assay. L-Arginine seems to be the major factor in retinal toxicity of commercial tPA (containing L-arginine). The formation of NO was markedly increased in mouse retinal cell cultures treated with tPA (containing L-arginine) or L-arginine. NO inhibitor reduced the cell death induced by commercially available tPA or L-arginine. Conclusions: This study suggests that L-arginine from commercial tPA (containing L-arginine) induces the majority of cell death in mouse retinal cell cultures and that its cytotoxicity may depend on the induction of NO.

Original languageEnglish
Pages (from-to)291-297
Number of pages7
JournalCurrent Eye Research
Volume30
Issue number4
DOIs
Publication statusPublished - 2005 Apr 1

Fingerprint

Tissue Plasminogen Activator
Arginine
Nitric Oxide
Cell Death
Cell Culture Techniques
Propidium
L-Lactate Dehydrogenase
Staining and Labeling
Intravitreal Injections
Primary Cell Culture
Fibrinolytic Agents
Conditioned Culture Medium
Neuroglia

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Oh, Hyun Sub ; Kwon, Oh W. ; Chung, In ; Lee, Sungchul ; Koh, Hyoung J. ; Lee, Sung Ho ; Lee, Joon H. / Retinal toxicity of commercial tissue plasminogen activator is mediated by the induction of nitric oxide in the mouse retinal primary cells. In: Current Eye Research. 2005 ; Vol. 30, No. 4. pp. 291-297.
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Retinal toxicity of commercial tissue plasminogen activator is mediated by the induction of nitric oxide in the mouse retinal primary cells. / Oh, Hyun Sub; Kwon, Oh W.; Chung, In; Lee, Sungchul; Koh, Hyoung J.; Lee, Sung Ho; Lee, Joon H.

In: Current Eye Research, Vol. 30, No. 4, 01.04.2005, p. 291-297.

Research output: Contribution to journalArticle

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N2 - Purpose: Tissue plasminogen activator (tPA) is an efficient thrombolytic agent, but the dose-dependent retinal toxicity of intravitreal injection of commercial tPA (containing L-arginine) has been reported. Here, we sought to investigate the mechanism of tPA-induced cell death in mouse retinal cell cultures and the role of nitric oxide (NO). Methods: Primary retinal cell cultures were maintained using glial conditioned medium (GCM) solution. Mouse retinal cell death was observed by using Hoechst-propidium iodide staining. Mouse retinal cell death was also measured by lactate dehydrogenase (LDH) assay. The formation of NO was measured using Griess reagent. Results: tPA-induced cell death was detected in mouse retinal cell cultures by Hoechst-propidium iodide staining or LDH assay. L-Arginine seems to be the major factor in retinal toxicity of commercial tPA (containing L-arginine). The formation of NO was markedly increased in mouse retinal cell cultures treated with tPA (containing L-arginine) or L-arginine. NO inhibitor reduced the cell death induced by commercially available tPA or L-arginine. Conclusions: This study suggests that L-arginine from commercial tPA (containing L-arginine) induces the majority of cell death in mouse retinal cell cultures and that its cytotoxicity may depend on the induction of NO.

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