Evidence map›Paper›PMID 24146542›Full record

Trial reportMolecular vision2013

Leukocytes from diabetic patients kill retinal endothelial cells: effects of berberine.

Pei Tian, Hongyan Ge, Haitao Liu, Timothy S Kern, Lingling Du, Linan Guan, Sheng Su, Ping Liu

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in Molecular vision, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.1field-weighted citation impact, top 7% 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

36 citing papers in PubMed, 45 citations in OpenAlex.

  1. Theophylline Inhibits Capillary Degeneration in Early Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026
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  19. Frontiers in pharmacology · 2019
    Review
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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

8 authors at 1 institution in 1 country.

Pei TianEye Hospital, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Hongyan Ge
Haitao Liu
Timothy S Kern
Lingling Du
Linan Guan
Sheng Su
Ping Liu
First Affiliated Hospital of Harbin Medical University · CN

Funding

STUDY OF DIABETIC RETINOPATHYR01EY000300 · NEI · UNIVERSITY OF WISCONSIN MADISON · PI KERN, TIMOTHY S · 1985 to 2013
$4.7M
Study of diabetic retinopathyR56EY000300 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI KERN, TIMOTHY S · 2009 to 2009
$353k
NEI NIH HHS EY00300NEI NIH HHS R01 EY000300NEI NIH HHS R56 EY000300
6 · The paper itself

Abstract

purposeAccumulating evidence in animals suggests that leukocytes are involved in the pathogenesis of diabetic retinopathy. The present study was designed to investigate whether leukocytes from diabetic patients could kill retinal endothelial cells and whether that cytotoxicity could be inhibited in vivo by administration of berberine.

methodsHuman retinal endothelial cells (HRECs) were cocultured (24 h) with leukocytes freshly isolated from nondiabetic and diabetic patients, and leukocyte-mediated death of HRECs was analyzed with flow cytometry. HRECs or leukocytes were incubated with antibodies against intercellular adhesion molecule-1(ICAM-1) or integrin beta-2, or with various concentrations of berberine. The protein expression levels of inflammatory factors were investigated using western blots, and activities of antioxidant enzymes and malondialdehyde content were examined as markers of oxidative stress. In addition, leukocytes were isolated from 28 diabetic patients with retinopathy and nondiabetic patients before and after 1 month in vivo therapy with berberine. The effects of the berberine on leukocyte-mediated killing of endothelial cells was again assessed.

resultsLeukocytes from diabetic patients induced more apoptosis of HRECs in a coculture system than did cells from nondiabetic patients, and this killing occurred primarily via direct cell-cell contact. Berberine inhibited the leukocyte-mediated killing of HRECs in vitro, the decrease in antioxidant enzyme activities, the nuclear translocation of nuclear factor kappa B, and the increase in intercellular adhesion molecule-1 and inducible nitric oxide synthase expression and malondialdehyde content in HRECs cultured in high glucose. Berberine also decreased integrin beta-2 expression of leukocytes in vitro and in vivo. Oral consumption of berberine for 1 month likewise inhibited the diabetes-induced increase in leukocyte-mediated killing of HRECs.

conclusionsOur findings suggest that leukocytes from diabetic patients kill retinal endothelial cells, and that berberine can inhibit this leukocyte-mediated killing of vascular endothelium. Coculture of leukocytes with HRECs might serve as a biomarker to study the role of leukocytes in the development of diabetic retinopathy, and the data are consistent with berberine being a therapy against diabetic retinopathy.

Indexed as

AnimalsApoptosisBerberineCD18 AntigensCell AdhesionDiabetes Mellitus, ExperimentalEndothelial CellsFemaleGlucoseHumansIntercellular Adhesion Molecule-1LeukocytesMaleMiddle AgedNF-kappa BOxidative StressBerberineCD18 AntigensGlucoseIntercellular Adhesion Molecule-1NF-kappa B

Identifiers

PMID24146542
PMCPMC3800284
OpenAlexW1548418968

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Registered trials

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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.