Omics · study · 2026
Intravitreal AAV delivery induces integrin-dependent ocular inflammation and activation of complement, antiviral and DNA damage responses
Listed in NCBI GEO
Intravitreal (IVT) AAV administration is a promising, non-invasive strategy for retinal transduction.
Description
However, IVT AAV delivery is often associated with dose-limiting inflammation, and corticosteroid treatment used to manage ocular uveitis is contra-indicated in some patients. Therefore, novel immunomodulatory strategies are needed, requiring further understanding of AAV-triggered immunity mechanisms.
Here we characterized immune responses to AAV2.7m8 in mice and pigs. IVT AAV delivery in mice revealed a key role for peripheral leukocytes in mediating ocular inflammation, while the response in pigs was predominantly driven by microglia activation and monocyte infiltration. Analysis of ocular humors identified MCP-1 and IP-10 as common AAV-induced inflammation markers in both species, with subsequent identification of MIP-1α, IL-6, and complement factor C3a as additional markers in pigs.
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We also detected DNA damage foci in treated retinas, including in regions exhibiting low or absent transgene expression, but with significant presence of vector genomes. Finally, snRNAseq detected significant transduction of retinal ganglion cells, identified astrocytes and microglia as the main sources of MCP-1 and IP-10, and revealed marked induction of interferon and pro-inflammatory signaling across all retinal cell populations.
Thus, our work identified new markers of ocular inflammation and potential targets to modulate AAV-induced uveitis.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE308nnn/GSE308982 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308982 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1333530 ncbi.nlm.nih.gov/bioproject/PRJNA1333530 ↗
project · from NCBI GEO
- PubMed 42099652 pubmed.ncbi.nlm.nih.gov/42099652 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Sus scrofa
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE308982 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9823 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |