{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:22:16Z","timestamp":1785424936663,"version":"3.56.0"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Illinois Society to Prevent Blindness"},{"DOI":"10.13039\/100013779","name":"Retina Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013779","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05n2ytn05","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04drjs621","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["EY031350"],"award-info":[{"award-number":["EY031350"]}]},{"name":"National Institute of Health","award":["EY001792"],"award-info":[{"award-number":["EY001792"]}]},{"award":["EY031350"],"award-info":[{"award-number":["EY031350"]}],"id":[{"id":"https:\/\/ror.org\/02hssy432","id-type":"ROR","asserted-by":"publisher"}]},{"award":["EY001792"],"award-info":[{"award-number":["EY001792"]}],"id":[{"id":"https:\/\/ror.org\/02hssy432","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The purpose of this project was to define gene expression changes associated with the acquisition and loss of resilience to diabetic retinopathy (RDR) in individual retinal cell types. A non-immune form of type 1 diabetes mellitus (DM) was induced by injecting male C57Bl6J mice with streptozotocin. Single-cell RNA sequencing was performed on retinas from mice that experienced DM for 5 or 15 days, along with retinas from age-matched, non-DM mice. The resulting data sets were analyzed to identify DM-associated differentially expressed genes and pathway enrichments after each duration of DM. We observed that acquisition of RDR, previously shown to arise after 5 days of DM was linked to altered expression of genes in a subset of retinal cells, mainly M\u00fcller cells. Pathway analysis indicated enhancement of numerous modes of protection, including reinforced neurovascular and structural homeostasis through phagocytosis, integrin signaling, and interferon-mediated defense. After 15 days of DM, when we previously showed that RDR is waning this pro-protection surge in gene expression subsided. We conclude that a duration of DM that is too short to cause diabetic retinopathy (DR) nonetheless evoked a profound change in the gene expression profile within a subset of retinal cell types. The nature and timing of this molecular shift indicated that it was not the preamble to DM-related damage that eventually develops. Rather, DM engaged numerous defense programs within M\u00fcller cells. The temporal alignment between RDR and activation of M\u00fcller cell-based defense provides a molecular foundation for the retina\u2019s transient ability to remain healthy in the face of DM.<\/jats:p>","DOI":"10.3390\/biom16040614","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:42:45Z","timestamp":1776771765000},"page":"614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resilience to Diabetic Retinopathy (RDR) Is Associated with a Pre-Retinopathy Transcriptional Program Induced by Diabetes"],"prefix":"10.3390","volume":"16","author":[{"given":"Janani","family":"Rajasekar","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-5445","authenticated-orcid":false,"given":"Maria Paula","family":"Zappia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8661-430X","authenticated-orcid":false,"given":"Maximilian A.","family":"McCann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3953-3739","authenticated-orcid":false,"given":"Maxim V.","family":"Frolov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1919-3327","authenticated-orcid":false,"given":"Andrius","family":"Kazlauskas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USA"},{"name":"Department of Physiology and Biophysics, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1161\/01.CIR.0000048892.83521.58","article-title":"Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: A \u201cset up\u201d for vascular disease","volume":"107","author":"Lakatta","year":"2003","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1172\/JCI64096","article-title":"Causes, consequences, and reversal of immune system aging","volume":"123","author":"Dorshkind","year":"2013","journal-title":"J. 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