{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:45:34Z","timestamp":1769507134585,"version":"3.49.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neurovascular degeneration results in vascular dysfunction, leakage, ischemia, and structural changes that can lead to significant visual impairment. We previously showed the protective effects of peptain-1, a 20 amino acid peptide derived from the \u03b1B-crystallin core domain, on retinal ganglion cells in two animal models of glaucoma. Here, we evaluated the ability of peptain-1 to block apoptosis of human retinal endothelial cells (HRECs) <jats:italic>in vitro<\/jats:italic> and retinal capillary degeneration in mice subjected to retinal ischemia\/reperfusion (I\/R) injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HRECs were treated with either peptain-1 or scrambled peptides (200 \u03bcg\/mL) for 3 h and a combination of proinflammatory cytokines (IFN-\u03b3 20 ng\/mL + TNF-\u03b1 20 ng\/mL+ IL-1\u03b2 20 ng\/mL) for additional 48 h. Apoptosis was measured with cleaved caspase-3 formation via western blot, and by TUNEL assay. C57BL\/6J mice (12 weeks old) were subjected to I\/R injury by elevating the intraocular pressure to 120 mmHg for 60 min, followed by reperfusion. Peptain-1 or scrambled peptide (0.5 \u03bcg) was intravitreally injected immediately after I\/R injury and 7 days later. One microliter of PBS was injected as vehicle control, and animals were euthanized on day 14 post-I\/R injury. Retinal capillary degeneration was assessed after enzyme digestion followed by periodic acid\u2013Schiff staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our data showed that peptain-1 entered HRECs and blocked proinflammatory cytokine-mediated apoptosis. Intravitreally administered peptain-1 was distributed throughout the retinal vessels after 4 h. I\/R injury caused retinal capillary degeneration. Unlike scrambled peptide, peptain-1 protected capillaries against I\/R injury. Additionally, peptain-1 inhibited microglial activation and reduced proinflammatory cytokine levels in the retina following I\/R injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our study suggests that peptain-1 could be used as a therapeutic agent to prevent capillary degeneration and neuroinflammation in retinal ischemia.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fncel.2024.1441924","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T05:20:11Z","timestamp":1722489611000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Peptain-1 blocks ischemia\/reperfusion-induced retinal capillary degeneration in mice"],"prefix":"10.3389","volume":"18","author":[{"given":"Mi-Hyun","family":"Nam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armaan","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rooban B.","family":"Nahomi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelle L.","family":"Carrillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarinda S.","family":"Hougen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram H.","family":"Nagaraj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.preteyeres.2006.10.003","article-title":"Crystallins in the eye: Function and pathology.","volume":"26","author":"Andley","year":"2007","journal-title":"Prog. 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