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Omics · study · 2026

Transcriptomic features of GFP+ RPE cells in Serpine-Gfp heterozygous mice at 2 months II

Listed in NCBI GEO

Heterogeneous degeneration of retinal pigment epithelium (RPE) leads to irreversible blindness in diseases associated with macular atrophy.

Description

However, the underlying mechanisms of regional RPE degeneration remain poorly understood. To address this gap, this study first identifies a novel RPE subpopulation through the spatial, transcriptomic, and functional analyses, thereby contributing to the understanding of the heterogeneity of degenerative RPE cells.

Specifically, omics analyses in human and macaque RPE reveal a peripheral RPE cell population with high SERPINE3 expression, while SERPINE3-GFP knock-in mice show comparable expression patterns. In addition, SMART-seq2 analysis further distinguishes transcriptomic profiles between GFP-positive and GFP-negative RPE cells. Under oxidative stress, SERPINE3 expression increases, and GFP-positive cells exhibit improved survival and reentry into the cell cycle.

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Notably, genetic studies indicate that SERPINE3 is essential for the oxidative stress resistance of GFP-positive cells. Moreover, loss of SERPINE3 results in regional RPE degeneration and increased microglial accumulation in aged mice. Mechanistically, proteinase screening and co-immunoprecipitation indicate that SERPINE3 targets Caspase-1.

Importantly, delivery of SERPINE3 via AAV-Serpine3 prevents RPE degeneration in a geographic atrophy disease model. These findings advance the understanding of RPE heterogeneous degeneration and highlight SERPINE3 as a novel protective factor with therapeutic potential for macular atrophy.

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From keywords
Life Sciences
Inferred from text
Disease 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE31080913 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title