Evidence map›Paper›PMID 40057214›Full record

ArticleThe journal of pain2025

Efficient removal of naturally-occurring lipofuscin autofluorescence in human nervous tissue using high-intensity white light.

Matthew R Sapio, Diana M King, Dragan Maric, Samay R Shah, Thomas L Talbot, Allison P Manalo, Pranavi Nara, Wenting Ma, Andre Ghetti, Christopher E Ramsden and 2 more

Abstract read
In one paragraph

Article in The journal of pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Glucagon-Like Peptide-1 Targets in the Human Nodose Ganglion.The Journal of comparative neurology · 2026
    Article
  4. Review
  5. Review
  6. Applications and development of in situ nucleic acid visualization techniques.Frontiers in bioengineering and biotechnology · 2026
    Review
  7. 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

12 authors.

Matthew R SapioDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: Matt.sapio@nih.gov.
Diana M KingDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Dragan MaricFlow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Samay R ShahDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Thomas L TalbotSection on Instrumentation, National Institute of Mental Health, Bethesda, MD 20892, USA.
Allison P ManaloDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Pranavi NaraDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Wenting MaDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Andre GhettiAnaBios Corporation, San Diego, CA 92109, USA.
Christopher E RamsdenLipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, NIH, 251 Bayview Blvd., Baltimore, MD 21224, USA; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Michael J IadarolaDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Andrew J MannesDepartment of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
The Pain Neural TranscriptomeZIAAT000017 · NCCIH · NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH · PI IADAROLA, MICHAEL J. · 2011 to 2013
$4.8M
Integrative And Molecular Studies Of Pain And Pain ControlZIACL090033 · CLC · CLINICAL CENTER · PI MANNES, ANDREW · 2014 to 2025
$0k
Mechanisms of Pain and Immune ProcessesZIACL090034 · CLC · CLINICAL CENTER · PI MANNES, ANDREW · 2014 to 2025
$0k
The Pain Neural TranscriptomeZIACL090035 · CLC · CLINICAL CENTER · PI MANNES, ANDREW · 2014 to 2025
$0k
Intramural NIH HHS Z99 CL999999Intramural NIH HHS ZIA AT000017Intramural NIH HHS ZIA CL090033Intramural NIH HHS ZIA CL090034Intramural NIH HHS ZIA CL090035NIA NIH HHS P30 AG019610NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

Background autofluorescence is enhanced in human tissue relative to small animals and presents a barrier to fully realizing the potential of novel multiplex methods in human studies. In particular, lipofuscin (LF) is an interfering pigment in multiplex fluorescence assays. Lipofuscin (LF) is a highly cross-linked aggregate of oxidized lipids, proteins, sugars, and metal ions that accumulates in lysosomes with age, and is strongly fluorescent across wavelengths that interfere with signals from common fluorophores. This is particularly apparent in dorsal root ganglion (DRG), where the LF deposits occupy up to 80% of the visible neuronal cytoplasm, affecting ∼45% of neurons in a typical section. This report describes a straightforward, scalable, pre-staining, white-light photobleaching method that near-totally reduces LF autofluorescence, and improves signal detection across the color spectrum without negatively impacting the multiplex fluorescence detection assay. It is effective for peripheral and central nervous system structures as well as pathological tissue such as Alzheimer's disease brain, which contains high levels of autofluorescent interference. This demonstrates the broad applicability to improving signal detection in human disease states to enable translational investigations in humans. This low-cost procedure can be rapidly implemented into existing research programs to increase the accessibility of high-plex fluorescent microscopy methodologies to enable direct-in-human research. PERSPECTIVE: White light photobleaching of lipofuscin before multiplex fluorescent in situ hybridization allows for rapid, near-total quenching of autofluorescence in healthy and diseased human nervous system tissue. Given the importance of direct-in-human investigations for validating translational studies and ensuring medical relevance, this simple yet powerful advance enables future anatomical investigations.

Indexed as

Ganglia, SpinalLightLipofuscinOptical ImagingFluorescenceHumansPhotobleachingLipofuscinAutofluorescenceDorsal root ganglionHuman tissueLipofuscinMultiplex in situ hybridization

Identifiers

PMID40057214
PMCPMC12074538

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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.