{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:10:35Z","timestamp":1789751435718,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,14]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01EY032542"],"award-info":[{"award-number":["R01EY032542"]}]},{"name":"NIH","award":["R01EY034531"],"award-info":[{"award-number":["R01EY034531"]}]},{"name":"NIH","award":["P30EY030413"],"award-info":[{"award-number":["P30EY030413"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Retinal ganglion cell (RGC) death following optic nerve injury is driven by transcriptional programs involved in apoptosis, neuroinflammation, and other regulated cell death pathways; however, the early transcriptomic changes initiating these processes remain poorly defined. We used rRNA-depleted total RNA sequencing to characterize early alterations in protein-coding genes, long noncoding RNAs (lncRNAs), and alternative splicing events in mouse retinas following optic nerve crush (ONC) and silicone oil-induced ocular hypertension under-detected (SOHU), prior to substantial RGC loss.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Whole retinas were collected 6 hours after ONC and 5 days after SOHU induction. Differentially expressed protein-coding genes and lncRNA-classified transcripts were identified using total RNA sequencing, followed by functional enrichment, lncRNA-associated pathway analysis, alternative splicing analysis, and fluorescent in situ hybridization (FISH) validation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    In SOHU retinas, hundreds of protein-coding genes and lncRNA-classified transcripts were differentially expressed, with enrichment of immune activation, extracellular matrix remodeling, complement, phagocytic signaling, and suppression of mitochondrial energy metabolism pathways. Similarly, in ONC retinas, many protein-coding genes and lncRNA-classified transcripts were differentially expressed, with a prominent chemokine, cytokine-dominant inflammatory response. FISH validation supported injury-associated upregulation of\n                    <jats:italic>Prss56<\/jats:italic>\n                    and\n                    <jats:italic>Lif<\/jats:italic>\n                    . Both injury models exhibited substantial transcript-level alterations, with widespread alternative splicing changes detected.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Early optic nerve injury induces rapid transcriptional changes involving protein-coding genes, lncRNAs, and transcript isoform regulation before substantial RGC loss. These findings highlight early alterations in both coding and noncoding RNA landscapes following retinal injury and provide a valuable resource of candidate genes and pathways for future validation in RGC degeneration and neuroprotection.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.08.750121","type":"posted-content","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:00:13Z","timestamp":1789434013000},"source":"Crossref","is-referenced-by-count":0,"title":["Total RNA Sequencing Reveals Early Coding, Noncoding, and Isoform-Level Transcriptomic Changes Following Traumatic and Glaucomatous Optic Nerve Injury"],"prefix":"10.64898","author":[{"given":"Noah C.","family":"Mathew","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin K.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Southwestern Medical Center"},{"name":"Department of Neuroscience, University of Texas Southwestern Medical Center"},{"name":"Peter O\u2019Donnell Jr. Brain Institute, University of Texas Southwestern Medical 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