{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:52:59Z","timestamp":1787028779000,"version":"build-2736575974"},"reference-count":86,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is both a poorly understood and devastating disease. Here, we analyze the physico-chemical forces at stake, including osmolarity, redox shift, and pressure due to inflammation. Hyperosmolarity plays a key role in diseases of the anterior segment of the eye such as glaucoma, cataracts or dry eyes, and corneal ulceration. However, its role in macular degeneration has been largely overlooked. Hyperosmolarity is responsible for metabolic shifts such as aerobic glycolysis which increases lactate secretion by Muller cells. Increased osmolarity will also cause neoangiogenesis and cell death. Because of its unique energetic demands, the macula is very sensitive to metabolic shifts. As a proof of concept, subretinal injection of drugs increasing hyperosmolarity such as polyethylene glycol causes neoangiogenesis and drusen-like structures in rodents. The link between AMD and hyperosmolarity is reinforced by the fact that treatments aiming to restore mitochondrial activity, such as lipoic acid and\/or methylene blue, have been experimentally shown to be effective. We suggest that metabolic shift, inflammation, and hyperosmolarity are hallmarks in the pathogenesis and treatment of AMD.<\/jats:p>","DOI":"10.3390\/life14091189","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T07:38:57Z","timestamp":1726817937000},"page":"1189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metabolic Shift and Hyperosmolarity Underlie Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"14","author":[{"given":"Laurent","family":"Schwartz","sequence":"first","affiliation":[{"name":"Assistance Publique des H\u00f4pitaux de Paris, 75610 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Assistance Publique des H\u00f4pitaux de Paris, 75610 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Henry","sequence":"additional","affiliation":[{"name":"Institut Le Bel, Universit\u00e9 Louis Pasteur, 67070 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Bakkar","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology, October University for Modern Sciences and Arts, Giza 12451, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1001\/jama.2023.26074","article-title":"Age-Related Macular Degeneration: A Review","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.ophtha.2017.05.035","article-title":"Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future","volume":"124","author":"Colijn","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.2147\/CIA.S143508","article-title":"Recent Developments in Age-Related Macular Degeneration: A Review","volume":"12","author":"Yassin","year":"2017","journal-title":"Clin. 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