Evidence map›Paper›PMID 34117982›Full record

ArticleJapanese journal of ophthalmology2021

Cytotoxic effects of alteplase, a recombinant tissue plasminogen activator, on human retinal pigment epithelial cells.

Shuhei Kimura, Yuki Morizane, Shinji Toshima, Yusuke Shiode, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Yuki Kanzaki, Fumio Shiraga

Abstract read
PubMed Publisher
In one paragraph

Article in Japanese journal of ophthalmology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Shuhei KimuraDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Yuki MorizaneDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan. moriza-y@okayama-u.ac.jp.
Shinji ToshimaDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Yusuke ShiodeDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Shinichiro DoiDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Kosuke TakahashiDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Ryo MatobaDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Yuki KanzakiDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Fumio ShiragaDepartment of Ophthalmology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama City, 7008558, Japan.
Okayama University · JP

Funding

Grant-in-Aid for Scientific Research(C) 16K11287
6 · The paper itself

Abstract

purposeTo evaluate the cytotoxic effects of alteplase, a recombinant tissue plasminogen activator, and its additives on human retinal pigment epithelial (hRPE) cells. STUDY

designLaboratory study.

methodsWe 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.

resultsAlteplase 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.

conclusionAlteplase can be cytotoxic to human RPE cells in a concentration- and time-dependent manner, with L-arginine being a possible causative factor.

Indexed as

Induced Pluripotent Stem CellsTissue Plasminogen ActivatorCells, CulturedEpithelial CellsHumansRetinal Pigment EpitheliumRetinal PigmentsVascular Endothelial Growth Factor ARetinal PigmentsTissue Plasminogen ActivatorVascular Endothelial Growth Factor ACytotoxicityHuman retinal pigment epithelial cellL-arginineSubmacular hemorrhageTissue plasminogen activator

Identifiers

PMID34117982
OpenAlexW3171817059

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.