{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:01:51Z","timestamp":1789549311380,"version":"build-2803163510"},"reference-count":94,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["EY033264"],"award-info":[{"award-number":["EY033264"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>In carbon monoxide (CO) therapy, CO is administered at low concentrations as a controlled solution; this approach enables the drug to achieve its cytoprotective properties, including anti-inflammatory, anti-apoptotic, and vasodilatory effects. CO therapy, initially reported to benefit cardiovascular and pulmonary conditions, is now used to treat ocular diseases in preclinical models. Carbon monoxide, a compound most famously known for its deleterious effects, is receiving more attention as a potential therapeutic candidate in ocular medicine. In a few studies, controlled low-dose CO therapy has shown anti-inflammatory and anti-apoptotic effects in various models of retinal disease (such as retinal ischemia-reperfusion injury, optic nerve crush, ocular hypertension, and autoimmune uveitis). We have summarized the clinical and preclinical findings, along with the potential therapeutic value of CO, in this review. In this context, the current and emerging CO delivery methods are also described, with a focus on exploring their safety, efficacy, and applicability in retinal disorders. Although a strong preclinical paradigm exists, clinical translation is limited at best. While some trials indicate acceptable safety levels for inhaled CO or CORM-based interventions, these results have not been robust or reproducible. Bridging this efficacy gap will rely on enhanced delivery strategies, stringent PK\/PD-informed dosing, and mechanism-specific endpoint-based trials.<\/jats:p>","DOI":"10.3390\/biom16020291","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:28:11Z","timestamp":1770910091000},"page":"291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Carbon Monoxide Therapy: Evidence and Prospects for Preventing and Treating Retinal Diseases"],"prefix":"10.3390","volume":"16","author":[{"given":"Mathew Reese","family":"Land","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marybeth","family":"Koepsell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Nussbaum","sequence":"additional","affiliation":[{"name":"Department of Music, Furman University, Greenville, SC 29613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Gomperts","sequence":"additional","affiliation":[{"name":"Hillhurst Biopharmaceuticals, Inc., Montrose, CA 91020, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3900-861X","authenticated-orcid":false,"given":"Andrew","family":"Gomperts","sequence":"additional","affiliation":[{"name":"Hillhurst Biopharmaceuticals, Inc., Montrose, CA 91020, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menaka C.","family":"Thounaojam","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, 1005 D.B. Todd Jr. Blvd, Nashville, TN 37208, USA"},{"name":"Meharry-Vanderbilt Alliance, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravirajsinh N.","family":"Jadeja","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, 1005 D.B. Todd Jr. Blvd, Nashville, TN 37208, USA"},{"name":"Meharry-Vanderbilt Alliance, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, 1005 D.B. Todd Jr. Blvd, Nashville, TN 37208, USA"},{"name":"Meharry-Vanderbilt Alliance, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kov\u00e1cs-Valasek, A., R\u00e1k, T., P\u00f6sty\u00e9ni, E., Csutak, A., and G\u00e1briel, R. (2023). Three Major Causes of Metabolic Retinal Degenerations and Three Ways to Avoid Them. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108728"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"04126","DOI":"10.7189\/jogh.13.04126","article-title":"Visual impairment and blindness caused by retinal diseases: A nationwide register-based study","volume":"13","author":"Zhou","year":"2023","journal-title":"J. Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wallsh, J.O., and Gallemore, R.P. (2021). 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