Evidence map›Paper›PMID 38718792›Full record

ArticleCell metabolism2024

Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy.

Tim F Dorweiler, Arjun Singh, Aditya Ganju, Todd A Lydic, Louis C Glazer, Richard N Kolesnick, Julia V Busik

Abstract read
In one paragraph

Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

35 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

7 authors.

Tim F DorweilerDepartment of Physiology, Michigan State University, East Lansing, MI 48824, USA; Vascular Biology Program, Boston Children's Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02113, USA.
Arjun SinghMemorial Sloan Kettering Cancer Center, Molecular Pharmacology Program, Sloan Kettering Institute New York, New York, NY 10065, USA.
Aditya GanjuMemorial Sloan Kettering Cancer Center, Molecular Pharmacology Program, Sloan Kettering Institute New York, New York, NY 10065, USA.
Todd A LydicDepartment of Physiology, Michigan State University, East Lansing, MI 48824, USA.
Louis C GlazerVitreo-Retinal Associates, Grand Rapids, MI 49546, USA; Ophthalmology, Michigan State University, East Lansing, MI 48824, USA.
Richard N KolesnickMemorial Sloan Kettering Cancer Center, Molecular Pharmacology Program, Sloan Kettering Institute New York, New York, NY 10065, USA. Electronic address: kolesnir@mskcc.org.
Julia V BusikDepartment of Physiology, Michigan State University, East Lansing, MI 48824, USA; Biochemistry and Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: julia-busik@ouhsc.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
Dyslipidemia and Diabetic RetinopathyR01EY016077 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI BUSIK, JULIA V · 2005 to 2025
$6.3M
LXR as a Novel Therapeutic Target in Diabetic RetinopathyR01EY025383 · NEI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BUSIK, JULIA V, GRANT, MARIA BARTOLOMEO · 2015 to 2024
$4.2M
Anti-ceramide immunotherapy for diabetic retinopathyR01EY030766 · NEI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Julia V Busik, Maria Bartolomeo Grant · 2019 to 2026
$2.4M
Ceramide-mediated mitochondrial damage in diabetic retinopathy investigated by novel microfluidic O2 sensing and bio-mimetic electrochemistryR01EY028049 · NEI · MICHIGAN STATE UNIVERSITY · PI BUSIK, JULIA V, PROSHLYAKOV, DENIS A · 2018 to 2021
$1.5M
NCI NIH HHS P30 CA008748NEI NIH HHS R01 EY016077NEI NIH HHS R01 EY025383NEI NIH HHS R01 EY028049NEI NIH HHS R01 EY030766
6 · The paper itself

Abstract

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1β induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death. Anti-ceramide antibodies abolish these events. Furthermore, intravitreal and systemic anti-ceramide antibodies protect from diabetic retinopathy in standardized rodent ischemia reperfusion and streptozotocin models. These data support (1) retinal endothelial ceramide as a diabetic retinopathy treatment target, (2) early-stage therapy of non-proliferative diabetic retinopathy to prevent progression, and (3) systemic diabetic retinopathy treatment; and they characterize diabetic retinopathy as a "ceramidopathy" reversible by anti-ceramide immunotherapy.

Indexed as

CeramidesDiabetic RetinopathyImmunotherapyAnimalsApoptosisDiabetes Mellitus, ExperimentalEndothelial CellsFemaleHumansInterleukin-1betaMaleMiceMice, Inbred C57BLMice, KnockoutRatsRetinaCeramidesInterleukin-1betaTumor Necrosis Factor-alphaapoptosisceramidediabetesdiabetic retinopathyendothelial cellIL-1βinflammationretinasphingomyelinaseTNFα

Identifiers

PMID38718792
PMCPMC11222062

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.