{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:49:17Z","timestamp":1760057357590,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research to Prevent Blindness, NY, to the Department of Ophthalmology, University of Colorado","award":["Gates Grubstake Award (R.H.N.)","T32 AG020494 (G.A.J.)","R01EY028179"],"award-info":[{"award-number":["Gates Grubstake Award (R.H.N.)","T32 AG020494 (G.A.J.)","R01EY028179"]}]},{"name":"Neurobiology of Aging and Alzheimer\u2019s Disease training","award":["Gates Grubstake Award (R.H.N.)","T32 AG020494 (G.A.J.)","R01EY028179"],"award-info":[{"award-number":["Gates Grubstake Award (R.H.N.)","T32 AG020494 (G.A.J.)","R01EY028179"]}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["Gates Grubstake Award (R.H.N.)","T32 AG020494 (G.A.J.)","R01EY028179"],"award-info":[{"award-number":["Gates Grubstake Award (R.H.N.)","T32 AG020494 (G.A.J.)","R01EY028179"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>This study evaluated the neuroprotective potential of peptain-1 conjugated to a cell-penetrating peptide (CPP-P1) in an ocular hypertension model of glaucoma. Brown Norway (BN) rats were subjected to intraocular pressure (IOP) elevation via intracameral injection of silicone oil (SO), with concurrent intravitreal injections of either CPP-P1 or a vehicle. Retinal cross-sections were analyzed for markers of neuroprotection, including cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB), growth-associated protein-43 (GAP43), synapsin-1 (SYN1), and superoxide dismutase 2 (SOD2). Hematoxylin and eosin staining was used to assess retinal-layer thickness. SO-treated rats exhibited significant reductions in the thickness of the inner nuclear layer (INL, 41%, p = 0.016), inner plexiform layer (IPL, 52%, p = 0.0002), and ganglion cell layer (GCL, 57%, p = 0.001). CPP-P1 treatment mitigated these reductions, preserving INL thickness by 32% (p = 0.059), IPL by 19% (p = 0.119), and GCL by 31% (p = 0.057). Increased levels of CREB (p = 0.17) and p-CREB (p = 0.04) were observed in IOP-elevated, CPP-P1-treated retinas compared to IOP-elevated, vehicle-treated retinas. Although overall GAP43 levels were low, there was a modest increase in expression within the IPL and GCL in SO- and CPP-P1-treated retinas (p = 0.15 and p = 0.09, respectively) compared to SO- and vehicle-treated retinas. SO injection reduced SYN1 expression in both IPL and GCL (p = 0.01), whereas CPP-P1 treatment significantly increased SYN1 levels in the IPL (p = 0.03) and GCL (p = 0.002). While SOD2 expression in the GCL was minimal across all groups, a trend toward increased expression was observed in CPP-P1-treated animals (p = 0.16). The SO model was replicated with SO removal after 7 days and monitored for 21 days followed by retinal flat-mount preparation to assess retinal ganglion cell (RGC) survival. A 42% loss in RGCs (p = 0.009) was observed in SO-injected eyes, which were reduced by approximately 37% (p = 0.03) with CPP-P1 treatment. These findings suggest that CPP-P1 is a promising neuroprotective agent that promotes retinal ganglion cell survival and the preservation of other retinal neurons, potentially through enhanced CREB signaling in a rat model of SO-induced ocular hypertension.<\/jats:p>","DOI":"10.3390\/biom15020219","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:36:32Z","timestamp":1738560992000},"page":"219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Neuroprotective Peptide Modulates Retinal cAMP Response Element-Binding Protein (CREB), Synapsin I (SYN1), and Growth-Associated Protein 43 (GAP43) in Rats with Silicone Oil-Induced Ocular Hypertension"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7330-269X","authenticated-orcid":false,"given":"Gretchen A.","family":"Johnson","sequence":"first","affiliation":[{"name":"North Texas Eye Research Institute, College of Biomedical and Translational Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"},{"name":"Department of Microbiology, Immunology, and Genetics, College of Biomedical and Translational Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raghu R.","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, College of Biomedical and Translational Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"},{"name":"Department of Pharmacology and Neuroscience, College of Biomedical and Translational Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram H.","family":"Nagaraj","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota L.","family":"Stankowska","sequence":"additional","affiliation":[{"name":"North Texas Eye Research Institute, College of Biomedical and Translational Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"},{"name":"Department of Microbiology, Immunology, and Genetics, College of Biomedical and Translational Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"ref_1","first-page":"e11686","article-title":"Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future","volume":"12","author":"Allison","year":"2020","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.preteyeres.2016.10.001","article-title":"Detection and measurement of clinically meaningful visual field progression in clinical trials for glaucoma","volume":"56","author":"Liebmann","year":"2017","journal-title":"Prog. 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