{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:13:06Z","timestamp":1789582386153,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Glaucoma is a chronic neurodegenerative disorder characterized by the selective vulnerability of retinal ganglion cells (RGCs), in which mitochondrial dysfunction, redox imbalance, and impaired bioenergetic signaling play central pathogenetic roles. Mitochondrial homeostasis in RGCs critically depends on maintaining intracellular NAD+ pools, which support oxidative phosphorylation, sirtuin-mediated deacetylation, and antioxidant gene expression. Nicotinamide riboside (NR), a potent NAD+ precursor, and berberine (BBR), an AMPK activator derived from Berberis aristata, have recently emerged as synergistic modulators of mitochondrial metabolism and oxidative stress resistance. Methods: This study retrospectively assessed clinical outcomes associated with combined nutraceutical supplementation of nicotinamide riboside (NR) and berberine (BBR) in patients with primary open-angle glaucoma undergoing stable topical hypotensive therapy. We have included a narrative review in the current literature regarding NAD+ biology, AMPK\u2013sirtuin signaling, and oxidative stress responses in retinal ganglion cell (RGC) degeneration. Due to the absence of comparator groups receiving only NR or only berberine in this retrospective cohort, the combined supplementation has been regarded as a biologically complementary strategy, and the potential for synergistic efficacy remains a subject for further investigation. Results: Translationally, a retrospective clinical cohort receiving combined NR and BBR supplementation showed functional stabilization of the visual field and structural preservation of the retinal nerve fiber layer over a six-month follow-up, in line with the proposed mitochondrial protective mechanisms. Conclusions: The clinical trends identified in this retrospective cohort have substantiated the translational significance of NR + BBR supplementation as a potential adjunctive approach in glaucoma management. NAD+ repletion and engagement of the AMPK\u2013SIRT\u2013NRF2 pathway may enhance mitochondrial resilience in RGCs. Collectively, these findings offer initial clinical evidence advocating for additional controlled studies on NR + berberine supplementation, while mechanistic interpretations have been derived from the existing literature and are hypothesis-generating.<\/jats:p>","DOI":"10.3390\/diseases14020056","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T16:12:37Z","timestamp":1770048757000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mitochondrial Resilience in Glaucoma: Targeting NAD+ Metabolism and Oxidative Stress in Retinal Ganglion Cell Degeneration with Nicotinamide Riboside and Berberine: Preliminary Clinical Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6710-2460","authenticated-orcid":false,"given":"Federico","family":"Visalli","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6807-9455","authenticated-orcid":false,"given":"Francesco","family":"Cappellani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0059-5253","authenticated-orcid":false,"given":"Giuseppe","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Spinello","sequence":"additional","affiliation":[{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-876X","authenticated-orcid":false,"given":"Alessandro","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7556-6952","authenticated-orcid":false,"given":"Ludovica","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2969-8610","authenticated-orcid":false,"given":"Matteo","family":"Capobianco","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"ref_1","first-page":"844","article-title":"Global data on visual impairment in the year 2002","volume":"82","author":"Resnikoff","year":"2004","journal-title":"Bull. 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