{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:53:59Z","timestamp":1777910039522,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      Glaucoma is a leading cause of irreversible blindness. Glaucomatous intraocular pressure (IOP) triggers deleterious effects, including gliosis, optic nerve (ON) axonal retraction, neurotrophic factor deprivation, inflammation, and other pathological events, leading to retinal ganglion cell (RGC) loss. Trophic factor impairment enhances RGC apoptosis susceptibility. Neuritin 1 (NRN1), a neurotrophic protein downstream of various neurotrophins, exhibited RGC protection and regeneration in axotomy models. We evaluated human recombinant NRN1's impact on human RGCs cultured in pressurized conditions within the\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      translaminar autonomous system to simulate glaucoma pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Human glaucomatous and non-glaucomatous donor eyes were obtained from eye banks according to the Declaration of Helsinki. Initially, we evaluated NRN1and RGC marker expression in glaucoma and non-glaucomatous retina to determine the NRN1 level and its association with RGC loss. Further, we evaluated NRN1\u2019s therapeutic potential by treating pressurized human eyes at normal and high IOP for seven days. Retina, ON, and conditioned medium were analyzed for RGC survival (\n                      <jats:italic toggle=\"yes\">THY1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">RBPMS<\/jats:italic>\n                      ), gliosis (\n                      <jats:italic toggle=\"yes\">GFAP<\/jats:italic>\n                      ), apoptosis (\n                      <jats:italic toggle=\"yes\">CASP3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CASP7<\/jats:italic>\n                      ), and extracellular matrix deposition (COLIV, FN) by qRT-PCR and western blotting. Paraphenylenediamine staining assessed ON axonal degeneration, whereas ex\n                      <jats:italic toggle=\"yes\">vivo<\/jats:italic>\n                      electroretinogram assessed retinal activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Glaucomatous retinas exhibited significant reductions in both NRN1 (\n                      <jats:italic toggle=\"yes\">*p<\/jats:italic>\n                      = 0.007,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5) and RGC marker expression (\n                      <jats:italic toggle=\"yes\">*p<\/jats:italic>\n                      = 0.04,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 5). NRN1 treatment reduced gliosis, extracellular matrix deposition, ON degeneration, and increased retinal activity in pressure-perfused eyes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our study confirms that NRN1 enhances human RGC survival and improves retinal function in degenerative conditions, substantiating it as a promising candidate for rescuing human RGCs from degeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2024.0041","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T12:51:57Z","timestamp":1720788717000},"page":"596-607","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Neuritin 1 Drives Therapeutic Preservation of Retinal Ganglion Cells in an\n                    <i>Ex Vivo<\/i>\n                    Human Glaucoma Model"],"prefix":"10.1177","volume":"40","author":[{"given":"Shahna S.","family":"Hameed","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole E.","family":"Bodi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan C.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tasneem P.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92971-w"},{"issue":"11","key":"e_1_3_7_3_2","first-page":"e11686","article-title":"Epidemiology of glaucoma: The past, present, and predictions for the future","volume":"12","author":"Allison K","year":"2020","unstructured":"Allison K, , Patel D, , Alabi O. Epidemiology of glaucoma: The past, present, and predictions for the future. Cureus, 2020; 12(11):e11686.","journal-title":"Cureus"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174314"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.09.005"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2017.1396617"},{"key":"e_1_3_7_7_2","first-page":"39","article-title":"Glial cell line-derived neurotrophic factor (GDNF) in patients with primary open-angle glaucoma and age-related cataract","volume":"28","author":"Shpak AA","year":"2022","unstructured":"Shpak AA, , Guekht AB, , Druzhkova TA, et al. Glial cell line-derived neurotrophic factor (GDNF) in patients with primary open-angle glaucoma and age-related cataract. 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