Evidence map›Paper›PMID 42223311›Full record

ArticleInvestigative ophthalmology & visual science2026

Revisiting the Molecular Architecture of Photoreceptor Ribbon Synapses Using Ultrastructure Expansion Microscopy.

Kei Takahashi, Natalia Dolgova, Raghavi Sudharsan, William A Beltran

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

4 authors.

Kei TakahashiDivision of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Natalia DolgovaDivision of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Raghavi SudharsanDivision of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
William A BeltranDivision of Experimental Retinal Therapies, Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

Funding

MODELS OF HEREDITY RETINAL DEGENERATIONR01EY006855 · NEI · UNIVERSITY OF PENNSYLVANIA · PI GUSTAVO David AGUIRRE, William A. Beltran · 1992 to 2026
$20.7M
Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
Translational Research for Retinal Degeneration TherapiesR01EY017549 · NEI · UNIVERSITY OF PENNSYLVANIA · PI BELTRAN, WILLIAM A. · 2007 to 2024
$14.1M
Retinal-adhesive thermoresponsive gel for AAV-mediated gene delivery to the outer retinaR01EY033049 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BELTRAN, WILLIAM A., BYRNE, LEAH · 2022 to 2025
$2.7M
Leica Stellaris 8 Falcon/FLIM for the PennVet Imaging CoreS10OD032305 · OD · UNIVERSITY OF PENNSYLVANIA · PI FREEDMAN, BRUCE D · 2023 to 2023
$842k
NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY006855NEI NIH HHS R01 EY017549NEI NIH HHS R01 EY033049NIH HHS S10 OD032305
6 · The paper itself

Abstract

Purpose: Immunofluorescence-based mapping of photoreceptor ribbon synapse nanostructure in extended formaldehyde-fixed specimens is challenging due to diffraction-limited resolution and fixation-associated loss of antigen accessibility that restrict reliable molecular localization and structural interpretation. To circumvent these physicochemical limitations, we tested whether ultrastructure expansion microscopy (U-ExM) could overcome these barriers and enable compartment-resolved structural and molecular analysis of photoreceptor ribbon synapses in archival canine retinal tissues. Methods: Cryosections from non-fixed and formaldehyde-fixed canine retinas were immunolabeled by conventional immunohistochemistry to screen 44 antibodies targeting 29 ribbon synapse-associated proteins. The same antibody set was then evaluated in U-ExM-processed formaldehyde-fixed cryosections. U-ExM datasets were analyzed using multi-orientation visualization, line-profile measurements, and three-dimensional segmentation for ribbon morphometry in mature and developing retinas. Results: Antibody performance differed markedly between non-fixed and formaldehyde-fixed sections, indicating fixation-dependent loss or gain of detectability across targets. U-ExM increased the fraction of compatible antibodies in formaldehyde-fixed tissue and improved effective spatial resolution within synaptic compartments. Multi-orientation visualization refined interpretation of rod spherule architecture and revealed multiple postsynaptic density 95 (PSD-95) subcellular sites of expression, including a postsynaptic pool in horizontal cell axon terminals within the invaginated compartment. U-ExM further enabled subcompartment-level visualization of active zone proteins, extended compartment-resolved mapping to the more complex cone pedicle, and supported quantitative ribbon measurements in mature retina and across postnatal development. Conclusions: U-ExM provides a practical framework for compartment-resolved molecular mapping and quantitative phenotyping of photoreceptor ribbon synapses in formaldehyde-fixed/frozen archival retinal tissue, enabling systematic comparisons across conditions and developmental stages in translational and comparative vision research.

Indexed as

Photoreceptor Cells, VertebrateSynapsesAnimalsDogsFormaldehydeImmunohistochemistryTissue FixationFormaldehyde

Identifiers

PMID42223311
PMCPMC13235756

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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.