Evidence map›Paper›PMID 39994686›Full record

ArticleImmunity & ageing : I & A2025

Secreted IgM deficiency alters the retinal landscape enhancing neurodegeneration associated with aging.

Sarah E Webster, Sydney M Les, Nico Deleon, Daken M Heck, Naomi L Tsuj, Michael J Clemente, Prentiss Jones, Nichol E Holodick

Abstract read
In one paragraph

Article in Immunity & ageing : I & A, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Sarah E WebsterCenter for Immunobiology, Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA. sarah.webster@wmed.edu.
Sydney M LesCenter for Immunobiology, Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA.
Nico DeleonCenter for Immunobiology, Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA.
Daken M HeckCenter for Immunobiology, Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA.
Naomi L TsujCenter for Immunobiology, Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA.
Michael J ClementeCenter for Immunobiology, Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA.
Prentiss JonesDepartment of Pathology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA.
Nichol E HolodickCenter for Immunobiology, Department of Investigative Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, 49007, USA.

Funding

Sex Determines Age-related Changes in the Repertoire and Function of Natural Antibodies Protective against Streptococcus pneumoniae with Increasing AgeR01AI154539 · NIAID · WESTERN MICHIGAN UNIV SCHOOL OF MEDICINE · PI HOLODICK, NICHOL ELIZABETH · 2020 to 2023
$1.5M
Sex Specific Regulation of B1 B Cell Self-Renewal and Natural Antibody ProductionF32AI174673 · NIAID · WESTERN MICHIGAN UNIV SCHOOL OF MEDICINE · PI WEBSTER, SARAH E · 2023 to 2025
$221k
National Institute of Allergy and Infectious Diseases 1R01AI154539-01National Institute of Allergy and Infectious Diseases F32AI174673-01A1NIAID NIH HHS F32 AI174673NIAID NIH HHS R01 AI154539
6 · The paper itself

Abstract

backgroundMaintenance of the retina, part of the central nervous system, and other structures in the eye is critical for vision preservation. Aging increases the prevalence of vision impairment, including glaucoma, macular degeneration, and diabetic retinopathy. The retina is primarily maintained by glial cells; however, recent literature suggests that lymphocytes may play a role in the homeostasis of central nervous system tissues. Natural antibodies are produced by B cells without infection or immunization and maintain tissue homeostasis. Here, we explored the potential role of natural immunoglobulin M (IgM) produced by B lymphocytes in maintaining retinal health during aging in mice.

resultsOur results indicate that the vitreous humor of both mice and humans contains IgM and IgG, suggesting that these immunoglobulins may play a role in ocular function. Furthermore, we observed that aged mice lacking secreted IgM (µs-/-) exhibited pronounced retinal degeneration, accompanied by reactive gliosis, and a proinflammatory cytokine environment. This contrasts with the aged wild-type counterparts, which retain their ability to secrete IgM and maintain a better retinal structure and anti-inflammatory environment. In addition to these findings, the absence of secreted IgM was associated with significant alterations in the retinal pigment epithelium, including disruptions to its morphology and signs of increased stress. This was further observed in changes to the blood-retinal-barrier, which is critical for regulation of retinal homeostasis.

conclusionsThese data suggest a previously unrecognized association between a lack of secreted IgM and alterations in the retinal microenvironment, leading to enhanced retinal degeneration during aging. Although the precise mechanism remains unclear, these findings highlight the potential importance of secreted IgM in processes that support retinal health over time. By increasing our understanding of ocular aging, these results show that there is a broader role for the immune system in retinal function and integrity in advanced age, opening new areas for the exploration of immune-related interventions in age-associated retinal conditions.

Indexed as

AgingCataractsIgMImmunoglobulinRetinaRetinal degenerationVitreous humor

Identifiers

PMID39994686
PMCPMC11849284

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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.