{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE342nnn/GSE342215/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE342215"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Single-Cell Spatial Transcriptomics Reveals Rewiring of RPE and Muller Glia Signaling toward Photoreceptors Following Outer Segment Disruption in Prph2C213Y Mice","description":"PRPH2 mutations cause inherited retinal dystrophies (IRDs), but how photoreceptor outer segment (OS) disruption reshapes the surrounding retina remains unclear. Using a heterozygous Prph2C213Y/+ mouse model generated by CRISPR/Cas9, we characterized age-related retinal pathology and responses of retinal pigment epithelium (RPE) and Muller glia. Independent age- and sex-matched cohorts were examined at 1, 3, and 6 months by electroretinography, optical coherence tomography, and fundus autofluorescence. Mutant mice showed rod dysfunction from 1 month, RPE dysfunction from 3 months, and cone dysfunction by 6 months, accompanied by progressive outer retinal thinning and hyperautofluorescent deposits. Histological and ultrastructural analyses revealed OS disorganization, shortened RPE microvilli, RPE monolayer remodeling, increased RPE autofluorescence, and reactive Muller gliosis. Single-cell spatial transcriptomics of wild-type and mutant retinas at 6 months resolved nine cell populations and identified RPE cells and Muller glia as prominently perturbed non-photoreceptor populations. RPE cells showed an epithelial-mesenchymal transition-related remodeling state linked to a candidate Nfib-Fstl1 module, whereas Muller glia showed activation of activator protein 1 (AP-1) regulons, including Fos, Fosl2, and Junb, with predicted targets Osmr, A2m, and Stat3. Cell-cell communication analyses indicated coordinated changes in neuroprotective, inflammatory, and matrix-related signaling from RPE cells and Muller glia toward photoreceptors. These findings indicate that PRPH2-associated retinal dystrophy is a multicellular process in which OS disruption drives coordinated RPE and Muller glial remodeling with potentially protective or pro-degenerative effects, and nominate the RPE Nfib-Fstl1 program, Muller glial AP-1 responses with predicted STAT3 involvement, and support-cell-derived growth factor signaling as candidate mutation-independent therapeutic targets.","dates":{"publication":"2026/08/13"},"accession":"GSE342215","cross_references":{"GSM":["GSM9925816","GSM9925817"],"GPL":["35959"],"GSE":["342215"],"taxon":["Mus musculus"]}}