{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:08:02Z","timestamp":1788944882458,"version":"build-2803163510"},"reference-count":14,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Proliferative diabetic retinopathy (PDR) is molecularly heterogeneous, but it is unclear whether immune-rich and endothelial-rich transcriptional patterns recur across retinal compartments. We integrated five public human transcriptomic datasets and analyzed PhysioNet CDED separately as the exploratory clinical context. GSE307925 served as the discovery cohort; GSE245561 and GSE165784 provided independent single-cell cross-cohort evaluation; GSE94019 provided CD31-enriched endothelial evaluation; and GSE160306 provided whole-retina disease-spectrum contextualization. In GSE307925, CD31-low and CD31-high samples separated strongly (PC1 61.5%; exact permutation p = 0.0013), with separation retained in all 12 leave-one-out analyses and under TMM normalization. In the two single-cell cohorts, the discovery-derived CD31-low signature localized to myeloid cells and the CD31-high signature to endothelial cells in all nine PDR donors (exact sign-test p = 0.00195 for each); the fibrotic\/ECM-remodeling core localized to stromal\/pericyte cells in all nine donors. In GSE94019, the fibrotic\/ECM-remodeling program was increased in PDR (p = 0.0028; q = 0.0084) and remained associated with PDR after adjustment for an independent pericyte-lineage score (\u03b2 = 1.473, 95% CI 0.758\u20132.189; p &lt; 0.001). In GSE160306, the discovery-derived CD31-low program showed a nominal association with advanced DR\/DME (\u03b2 = 0.306, 95% CI 0.026\u20130.585; p = 0.032; q = 0.085). These findings support compartment-dependent molecular enrichment rather than fixed binary patient subtypes.<\/jats:p>","DOI":"10.3390\/biology15181581","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:05:43Z","timestamp":1788941143000},"page":"1581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Compartment-Specific Immune, Endothelial, and Fibrotic Programs in Diabetic Retinopathy: An Integrative Multi-Cohort Transcriptomic Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1414-9423","authenticated-orcid":false,"given":"Ece","family":"Celik","sequence":"first","affiliation":[{"name":"Division of Allergy and Clinical Immunology, Department of Chest Diseases, Faculty of Medicine, Trakya University, 22030 Edirne, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Buket","family":"Yilmaz Bulbul","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Trakya University, 22030 Edirne, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Burak","family":"Andac","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Trakya University, 22030 Edirne, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7364-370X","authenticated-orcid":false,"given":"Mehmet","family":"Celik","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Trakya University, 22030 Edirne, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16012","DOI":"10.1038\/nrdp.2016.12","article-title":"Diabetic retinopathy","volume":"2","author":"Wong","year":"2016","journal-title":"Nat. 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