{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:11:43Z","timestamp":1789776703141,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T00:00:00Z","timestamp":1682726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chungbuk National University","award":["HI22C1650"],"award-info":[{"award-number":["HI22C1650"]}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI22C1650"],"award-info":[{"award-number":["HI22C1650"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12\u201317 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9\u20134.5 \u00d7 108 exosomes in 10 \u03bcL\/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 \u03bcg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.<\/jats:p>","DOI":"10.3390\/ijms24098073","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T13:54:46Z","timestamp":1682949286000},"page":"8073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma"],"prefix":"10.3390","volume":"24","author":[{"given":"Hye-Rim","family":"Seong","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"},{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Ho","family":"Noh","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"},{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangryong","family":"Park","sequence":"additional","affiliation":[{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumin","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok-Jin","family":"Hong","sequence":"additional","affiliation":[{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah-young","family":"Lee","sequence":"additional","affiliation":[{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongho","family":"Geum","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-7620","authenticated-orcid":false,"given":"Soon-Cheol","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biology Education, Korea National University of Education, Cheongju 28173, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Myoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehn-Kyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-041X","authenticated-orcid":false,"given":"Yun-Bae","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea"},{"name":"Central Research Institute, Designed Cells Co., Ltd., Cheongju 28576, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide. 1990\u20132010: A systematic analysis","volume":"1","author":"Bourne","year":"2013","journal-title":"Lancet Glob. 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