Evidence map›Paper›PMID 40484363›Full record

ArticleExperimental eye research2025

AAV2.7m8 transduction of stage 2 human retinal organoids induces highly variable responses in innate and inflammatory gene expression and cytokine secretion.

Monica M Sauter, Hongyu Rao Noel, Divya Sinha, Emma C Nelson, Mai N Xiong, David M Gamm, Curtis R Brandt

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental eye research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
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  3. Review
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.

Monica M SauterDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Hongyu Rao NoelDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Divya SinhaMcPherson Eye Research Institute, Wisconsin Institutes for Medical Research (WIMR), 1111 Highland Avenue, 9431, Madison, WI, 53705, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Emma C NelsonWaisman Center, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Mai N XiongWaisman Center, University of Wisconsin-Madison, Madison, WI, 53706, USA.
David M GammDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA; McPherson Eye Research Institute, Wisconsin Institutes for Medical Research (WIMR), 1111 Highland Avenue, 9431, Madison, WI, 53705, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Curtis R BrandtDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA; Department of Medical Microbiology and Immunology University of Wisconsin-Madison, Madison, WI, 53706, USA; McPherson Eye Research Institute, Wisconsin Institutes for Medical Research (WIMR), 1111 Highland Avenue, 9431, Madison, WI, 53705, USA. Electronic address: crbrandt@wisc.edu.

Funding

UW Vision Research Core - Administrative CoreP30EY016665 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI AKIHIRO IKEDA · 2005 to 2026
$12.6M
Enhancing Basic and Translational Vision Research Using AnimalsS10OD026957 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI BRANDT, CURTIS R · 2019 to 2019
$529k
NEI NIH HHS P30 EY016665NIH HHS S10 OD026957
6 · The paper itself

Abstract

The preclinical evaluation of recombinant AAV (rAAV) gene therapy vectors should consider host innate and inflammatory immune responses which can cause harmful ocular inflammation and decrease the efficiency of transgene delivery. In this study we determined which cell types expressed the transgene following transduction of 75-day-old human pluripotent stem cell (hPSC)-derived retinal organoids (RO) with the gene delivery vector AAV2.7m8-CAG-EGFP (AAVGFP). We then examined the changes in RO inflammatory gene expression and cytokine secretion following AAVGFP transduction. Our results indicated that RO cell types including photoreceptors (PR), retinal progenitor cells (RPCs), retinal ganglion cells (RGC), horizontal cells, and amacrine cells were transduced by AAVGFP. PCR array analysis following AAVGFP RO transduction detected up regulation of innate and adaptive immune response genes including chemokine (CC) genes, cluster of differentiation (CD) genes, interleukin (IL) genes, and transcription factors. The changes in gene expression following RO transduction varied drastically depending on the manufacturer and the production lot of AAVGFP, and were also not consistent between RO batches transduced with the same lot of AAVGFP. Analysis of RO supernatants indicated that several pro- and anti-inflammatory cytokines including sCD40L, IL-4, IL-6, IL-10, IL-13, IL-17A and MCP-1 were secreted following AAVGFP transduction, but the secretion pattern of these cytokines varied between transductions. These data indicate that intermediate-stage differentiating human ROs derived from the same hPSC line have highly variable responses to rAAV gene delivery vectors.

Indexed as

CytokinesDependovirusGene Expression RegulationImmunity, InnateOrganoidsRetinaTransduction, GeneticCells, CulturedGenetic TherapyGenetic VectorsHumansCytokinesCytokinesInflammationInnate immune responseOcular gene therapyRecombinant AAVRetinal organoids

Identifiers

PMID40484363
PMCPMC12229142

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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.