Evidence map›Paper›PMID 40576434›Full record

ArticleInvestigative ophthalmology & visual science2025

The Sialome of the Retina, Alteration in Age-Related Macular Degeneration Pathology, and Potential Impacts on Complement Factor H.

Jaclyn Swan, Christopher B Toomey, Max Bergstrand, Hector A Cuello, Jesse Robie, Hai Yu, Yue Yuan, Anoopjit Singh Kooner, Xi Chen, Jutamas Shaughnessy and 3 more

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Glycosylation of the retina.Biochemical Society transactions · 2026
    Review
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Jaclyn SwanDepartment of Pathology, University of California - San Diego, La Jolla, California, United States.
Christopher B ToomeyShiley Eye Institute, Viterbi Family Department of Ophthalmology University of California - San Diego, La Jolla, California, United States.
Max BergstrandDepartment of Pathology, University of California - San Diego, La Jolla, California, United States.
Hector A CuelloGlycobiology Research and Training Center, University of California - San Diego, La Jolla, California, United States.
Jesse RobieDepartment of Pathology, University of California - San Diego, La Jolla, California, United States.
Hai YuDepartment of Chemistry, University of California - Davis, Davis, California, United States.
Yue YuanDepartment of Chemistry, University of California - Davis, Davis, California, United States.
Anoopjit Singh KoonerDepartment of Chemistry, University of California - Davis, Davis, California, United States.
Xi ChenDepartment of Chemistry, University of California - Davis, Davis, California, United States.
Jutamas ShaughnessyDivision of Infectious Diseases and Immunology, University of Massachusetts, Chan Medical School, Worcester, Massachusetts, United States.
Sanjay RamDivision of Infectious Diseases and Immunology, University of Massachusetts, Chan Medical School, Worcester, Massachusetts, United States.
Ajit VarkiGlycobiology Research and Training Center, University of California - San Diego, La Jolla, California, United States.
Pascal GagneuxDepartment of Pathology, University of California - San Diego, La Jolla, California, United States.

Funding

Medical Scientist Training Program Training GrantT32GM145449 · NIGMS · DUKE UNIVERSITY · PI Christopher D Kontos · 2022 to 2026
$6.6M
Supplement: Exploring the biology of O-acetyl sialic acids using stable synthetic mimicsR01AI130684 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CHEN, XI, VARKI, AJIT P · 2017 to 2020
$2.3M
Role of Bruch Membrane Heparan Sulfate in Drusenogenesis in Age-Related Macular DegenerationK08EY035322 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Christopher B Toomey · 2024 to 2026
$764k
Bruch's Membrane-On-A-Chip to Study Drusen Formation in AMDR21EY037260 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TOOMEY, CHRISTOPHER B · 2025 to 2025
$639k
NEI NIH HHS K08 EY035322NEI NIH HHS R21 EY037260NIAID NIH HHS R01 AI130684NIGMS NIH HHS T32 GM145449
6 · The paper itself

Abstract

Purpose: Little is known about sialic acids of the human retina, despite their integral role in self /non-self-discrimination by complement factor H (FH), the alternative complement pathway inhibitor. Methods: A custom sialoglycan microarray was used to characterize the sialic acid-binding specificity of native FH or recombinant molecules where IgG Fc was fused to FH domains 16 to 20 (which contains a sialic acid-binding site), domains 6 and 7 (which contains a glycosaminoglycan-binding site), or the FH-related proteins (FHRs) 1 and 3. We analyzed macular and peripheral retinal tissue from postmortem ocular globes for the amount, type, and presentation (glycosidic linkage type) of sialic acid in individuals with age-related macular degeneration (AMD) and age-matched controls using fluorescent lectins and antibodies to detect sialic acid and endogenous FH. Released sialic acids from neural retina, retinal pigmented epithelium (RPE) cells, and the Bruch's membrane (BrM) were labeled with 1,2-diamino-4,5-methylenedioxybenzene-2HCl (DMB), separated and quantified by high-performance liquid chromatography (HPLC). Results: Both native FH and the recombinant FH domains 16 to 20 recognized Neu5Ac and Neu5Gc that is α2-3-linked to the underlying galactose. 4-O-Actylation of sialic acid and sulfation of GlcNAc did not inhibit binding. Different linkage types of sialic acid were localized at different layers of the retina. The greatest density of α2-3-sialic acid, which is the preferred ligand of FH, did not colocalize with endogenous FH. The level of sialic acids at the BrM/choroid interface of the macula and peripheral retina of individuals with AMD were significantly reduced. Conclusions: The sialome of the human retina is altered in AMD. This may affect FH binding and, consequently, alternative complement pathway regulation.

Indexed as

Complement Factor HMacular DegenerationN-Acetylneuraminic AcidRetinaSialic AcidsAgedAged, 80 and overBruch MembraneFemaleHumansMaleMiddle AgedRetinal Pigment EpitheliumCFH protein, humanComplement Factor HN-Acetylneuraminic AcidSialic Acids

Identifiers

PMID40576434
PMCPMC12212450

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.