論文 - 詳細
| RRC ID | 68135 |
|---|---|
| 著者 | Kimura S, Morizane Y, Toshima S, Shiode Y, Doi S, Takahashi K, Matoba R, Kanzaki Y, Shiraga F. |
| タイトル | Cytotoxic effects of alteplase, a recombinant tissue plasminogen activator, on human retinal pigment epithelial cells. |
| ジャーナル | Jpn J Ophthalmol |
| Abstract |
PURPOSE:To evaluate the cytotoxic effects of alteplase, a recombinant tissue plasminogen activator, and its additives on human retinal pigment epithelial (hRPE) cells. STUDY DESIGN:Laboratory study. METHODS:We evaluated the cytotoxic effects of alteplase on human fetal RPE (hfRPE) cells, human induced pluripotent stem cell-derived RPE (hiPS-RPE), and ARPE-19 cells, as well as the cytotoxic effects of L-arginine and polysorbate 80, two additives of alteplase, on hfRPE cells. The effects of alteplase on the production of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) from hfRPE cells and the transepithelial resistance (TER) of hiPS-RPE cells were also assessed. The type of cell death induced by alteplase was investigated using ethidium homodimer III and FITC-Annexin V staining and terminal transferase deoxyuridine triphosphatase nick-end labeling. RESULTS:Alteplase reduced the viability of hfRPE cells significantly in a dose- and time-dependent manner. The reaction of hiPS-RPE and ARPE19 cells to alteplase was similar to that of hfRPE cells. Out of L-arginine and polysorbate 80, only treatment with L-arginine significantly reduced the viability of hfRPE cells. Alteplase (83 μg/ml, 6 h) had no significant effect on the production of VEGF and PEDF from hfRPE cells. Alteplase decreased the TER of hiPS-RPE cells in a dose- and time-dependent manner and induced necrosis as the type of cell death. CONCLUSION:Alteplase can be cytotoxic to human RPE cells in a concentration- and time-dependent manner, with L-arginine being a possible causative factor. |
| 巻・号 | 65(5) |
| ページ | 731-739 |
| 公開日 | 2021-9-1 |
| DOI | 10.1007/s10384-021-00848-2 |
| PII | 10.1007/s10384-021-00848-2 |
| PMID | 34117982 |
| MeSH | Cells, Cultured Epithelial Cells Humans Induced Pluripotent Stem Cells* Retinal Pigment Epithelium Retinal Pigments Tissue Plasminogen Activator* / toxicity Vascular Endothelial Growth Factor A |
| IF | 1.725 |
| リソース情報 | |
| ヒト・動物細胞 | 454E2(HPS0077) |