{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:54:45Z","timestamp":1791572085318,"version":"4.3.4"},"reference-count":99,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001381","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS-2021-NR060133"],"award-info":[{"award-number":["RS-2021-NR060133"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nicotinamide adenine dinucleotide (NAD+) boosting can sustain energy metabolism and neurovascular stability in the retinal tissue. Depletion of NAD+ is linked to the development of pathological retinal conditions, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction, oxidative stress, and inflammation occur in these diseases. This review summarizes substantial evidence of therapeutic NAD+ boosters, including nicotinamide, nicotinamide mononucleotide, or nicotinamide riboside. They help improve mitochondrial function and lessen neurovascular injury. We also emphasize the importance of natural products and sirtuins in facilitating cytoprotective effects through the regulation of mitochondrial balance and inflammation. Developments in drug delivery methods, such as nanoparticle encapsulation and targeted eye treatments, are promising for enhancing the bioavailability and effectiveness of NAD+ boosters. The novelty of this work is its combination of mechanistic insights regarding NAD+ metabolism with efficacy data from preclinical studies. Furthermore, natural products may work together to boost their therapeutic effects against retinal damage. Together, our review article highlights NAD+ metabolism as a potential therapeutic target for addressing retinal degeneration and maintaining vision in aging, neurologic disorders, and various metabolic diseases, including diabetes.<\/jats:p>","DOI":"10.3390\/ijms262210923","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"10923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Preventive and Protective Effects of Nicotinamide Adenine Dinucleotide Boosters in Aging and Retinal Diseases"],"prefix":"10.3390","volume":"26","author":[{"given":"Saba","family":"Noreen","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-Gil, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4548-1285","authenticated-orcid":false,"given":"Soon Sung","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-Gil, Chuncheon 24252, Republic of Korea"},{"name":"Korean Institute of Nutrition, Hallym University, 1 Hallymdeahak-Gil, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-9039","authenticated-orcid":false,"given":"Deokho","family":"Lee","sequence":"additional","affiliation":[{"name":"Korean Institute of Nutrition, Hallym University, 1 Hallymdeahak-Gil, Chuncheon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.brainres.2017.07.025","article-title":"Retinal metabolism: A comparative look at energetics in the retina","volume":"1672","author":"Country","year":"2017","journal-title":"Brain Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.1074\/jbc.M115.698985","article-title":"Phototransduction influences metabolic flux and nucleotide metabolism in mouse retina","volume":"291","author":"Du","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Choi, Y.K. (2022). An altered neurovascular system in aging-related eye diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214104"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100858","DOI":"10.1016\/j.preteyeres.2020.100858","article-title":"Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration","volume":"79","author":"Kaarniranta","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.preteyeres.2015.06.002","article-title":"Molecular pathogenesis of retinal and choroidal vascular diseases","volume":"49","author":"Campochiaro","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s42399-025-01936-x","article-title":"Multi-Target Drug Strategies in the Treatment of Diabetic Retinopathy","volume":"7","author":"Julius","year":"2025","journal-title":"SN Compr. Clin. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.cmet.2016.05.006","article-title":"CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism","volume":"23","author":"Tarrago","year":"2016","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/s42255-020-00298-z","article-title":"CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels","volume":"2","author":"Chini","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"P\u00f6sty\u00e9ni, E., G\u00e1briel, R., and Kov\u00e1cs-Valasek, A. (2024). Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Diabetic Retinopathy: An Attractive but Elusive Choice for Drug Development. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16101320"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.aac4854","article-title":"NAD+ in aging, metabolism, and neurodegeneration","volume":"350","author":"Verdin","year":"2015","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41580-020-00313-x","article-title":"NAD+ metabolism and its roles in cellular processes during ageing","volume":"22","author":"Covarrubias","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Massudi, H., Grant, R., Braidy, N., Guest, J., Farnsworth, B., and Guillemin, G.J. (2012). Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042357"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tovar-Palacio, C., Noriega, L.G., and Mercado, A. (2022). Potential of polyphenols to restore SIRT1 and NAD+ metabolism in renal disease. Nutrients, 14.","DOI":"10.3390\/nu14030653"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.cell.2013.06.016","article-title":"The NAD+\/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling","volume":"154","author":"Mouchiroud","year":"2013","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.preteyeres.2018.06.002","article-title":"NAD+ and sirtuins in retinal degenerative diseases: A look at future therapies","volume":"67","author":"Lin","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.cmet.2017.11.002","article-title":"NAD+ intermediates: The biology and therapeutic potential of NMN and NR","volume":"27","author":"Yoshino","year":"2018","journal-title":"Cell Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12948","DOI":"10.1038\/ncomms12948","article-title":"Nicotinamide riboside is uniquely and orally bioavailable in mice and humans","volume":"7","author":"Trammell","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6881322","DOI":"10.1155\/2022\/6881322","article-title":"PARP-1 Is a Potential Marker of Retinal Photooxidation and a Key Signal Regulator in Retinal Light Injury","volume":"2022","author":"Li","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bbrc.2019.03.199","article-title":"The NADase CD38 is induced by factors secreted from senescent cells providing a potential link between senescence and age-related cellular NAD+ decline","volume":"513","author":"Chini","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"390","DOI":"10.14336\/AD.2023.0516-1","article-title":"SARM1 Promotes Neurodegeneration and Memory Impairment in Mouse Models of Alzheimer\u2019s Disease","volume":"15","author":"Miao","year":"2024","journal-title":"Aging Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Khan, A.H., Chowers, I., and Lotery, A.J. (2023). Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment. Cells, 12.","DOI":"10.3390\/cells12131708"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.cell.2013.11.037","article-title":"Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging","volume":"155","author":"Gomes","year":"2013","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and aging: Signaling pathways and intervention therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1167\/iovs.66.4.14","article-title":"Nicotinamide Riboside Mitigates Retinal Degeneration by Suppressing Damaged DNA-Stimulated Microglial Activation and STING-Mediated Pyroptosis","volume":"66","author":"Zhu","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Guo, L., Choi, S., Bikkannavar, P., and Cordeiro, M.F. (2022). Microglia: Key Players in Retinal Ageing and Neurodegeneration. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.804782"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Croft, T., Venkatakrishnan, P., and Lin, S.-J. (2020). NAD+ metabolism and regulation: Lessons from yeast. Biomolecules, 10.","DOI":"10.3390\/biom10020330"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.cmet.2018.03.016","article-title":"A potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD+ decline","volume":"27","author":"Chini","year":"2018","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Singh, M., Negi, R., Vinayagam, R., Kang, S.G., and Shukla, P. (2024). Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics. Medicina, 60.","DOI":"10.3390\/medicina60101647"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.mam.2012.06.003","article-title":"Animal models of age related macular degeneration","volume":"33","author":"Pennesi","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5961123","DOI":"10.1155\/2022\/5961123","article-title":"Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE","volume":"2022","author":"Ren","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14710","DOI":"10.1073\/pnas.1604572113","article-title":"Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium","volume":"113","author":"Du","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.stem.2016.12.015","article-title":"Nicotinamide Ameliorates Disease Phenotypes in a Human iPSC Model of Age-Related Macular Degeneration","volume":"20","author":"Saini","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.18632\/aging.101469","article-title":"Loss of NAMPT in aging retinal pigment epithelium reduces NAD(+) availability and promotes cellular senescence","volume":"10","author":"Jadeja","year":"2018","journal-title":"Aging"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wondmeneh, T.G., and Mohammed, J.A. (2024). Prevalence of diabetic retinopathy and its associated risk factors among adults in Ethiopia: A systematic review and meta-analysis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-78596-9"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"He, W., Tang, P., and Lv, H. (2025). Targeting oxidative stress in diabetic retinopathy: Mechanisms, pathology, and novel treatment approaches. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1571576"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Seo, H., Park, S.J., and Song, M. (2025). Diabetic Retinopathy (DR): Mechanisms, Current Therapies, and Emerging Strategies. Cells, 14.","DOI":"10.3390\/cells14050376"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/978-1-4614-3209-8_35","article-title":"Hypoxia-inducible factor (HIF)\/vascular endothelial growth factor (VEGF) signaling in the retina","volume":"801","author":"Kurihara","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2302\/kjm.2017-0002-IR","article-title":"Roles of Hypoxia Response in Retinal Development and Pathophysiology","volume":"67","author":"Kurihara","year":"2018","journal-title":"Keio J. Med."},{"key":"ref_41","first-page":"5071","article-title":"Effects of HIF-1\u03b1 on diabetic retinopathy angiogenesis and VEGF expression","volume":"22","author":"Zhang","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tomita, Y., Lee, D., Tsubota, K., and Kurihara, T. (2020). PPAR\u03b1 Agonist Oral Therapy in Diabetic Retinopathy. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100433"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jung, K.I., Han, J.-S., and Park, C.K. (2022). Neuroprotective effects of nicotinamide (vitamin B3) on neurodegeneration in diabetic rat retinas. Nutrients, 14.","DOI":"10.3390\/nu14061162"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Popescu, R.G., Dinischiotu, A., Soare, T., Vlase, E., and Marinescu, G.C. (2024). Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052594"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.clnesp.2023.04.031","article-title":"Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects","volume":"56","author":"Yamane","year":"2023","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"117411","DOI":"10.1016\/j.bone.2025.117411","article-title":"The protection of nicotinamide riboside against diabetes mellitus-induced bone loss via OXPHOS","volume":"193","author":"Gao","year":"2025","journal-title":"Bone"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1016\/j.celrep.2019.07.043","article-title":"Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures","volume":"28","author":"Elhassan","year":"2019","journal-title":"Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"117066","DOI":"10.1016\/j.taap.2024.117066","article-title":"Nicotinamide riboside activates SIRT3 to prevent paclitaxel-induced peripheral neuropathy","volume":"491","author":"Sun","year":"2024","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1093\/gerona\/glad106","article-title":"Dietary supplementation with NAD+-boosting compounds in humans: Current knowledge and future directions","volume":"78","author":"Freeberg","year":"2023","journal-title":"J. Gerontol. Ser. A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41514-023-00134-0","article-title":"The use of a systems approach to increase NAD+ in human participants","volume":"10","author":"Henderson","year":"2024","journal-title":"NPJ Aging"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1016\/j.advnut.2023.08.008","article-title":"The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: An Update","volume":"14","author":"Song","year":"2023","journal-title":"Adv. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.neuron.2021.02.009","article-title":"SARM1 is a metabolic sensor activated by an increased NMN\/NAD(+) ratio to trigger axon degeneration","volume":"109","author":"Figley","year":"2021","journal-title":"Neuron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.neuron.2021.03.021","article-title":"An NAD+\/NMN balancing act by SARM1 and NMNAT2 controls axonal degeneration","volume":"109","author":"Waller","year":"2021","journal-title":"Neuron"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tang, B.L. (2017). Is SIRT6 activity neuroprotective and how does it differ from SIRT1 in this regard?. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00165"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-022-01257-8","article-title":"The sirtuin family in health and disease","volume":"7","author":"Wu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40478-023-01513-0","article-title":"NAD salvage pathway machinery expression in normal and glaucomatous retina and optic nerve","volume":"11","author":"Tribble","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chaqour, B., Rossman, J.B., Meng, M., Dine, K.E., Ross, A.G., and Shindler, K.S. (2025). SIRT1-based therapy targets a gene program involved in mitochondrial turnover in a model of retinal neurodegeneration. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-97456-8"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"745","DOI":"10.2337\/db17-0996","article-title":"Sirt1: A Guardian of the Development of Diabetic Retinopathy","volume":"67","author":"Mishra","year":"2018","journal-title":"Diabetes"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1167\/tvst.12.4.20","article-title":"Intravitreal Administration of AAV2-SIRT1 Reverses Diabetic Retinopathy in a Mouse Model of Type 2 Diabetes","volume":"12","author":"Vieira","year":"2023","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41514-017-0017-8","article-title":"Neuroprotective role of retinal SIRT3 against acute photo-stress","volume":"3","author":"Ban","year":"2017","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"114320","DOI":"10.1016\/j.yexcr.2024.114320","article-title":"SIRT3 mitigates high glucose-induced damage in retinal microvascular endothelial cells via OPA1-mediated mitochondrial dynamics","volume":"444","author":"Shi","year":"2025","journal-title":"Exp. Cell Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109015","DOI":"10.1016\/j.exer.2022.109015","article-title":"Effect of Sirt3 on retinal pigment epithelial cells in high glucose through Foxo3a\/PINK1-Parkin pathway mediated mitophagy","volume":"218","author":"Huang","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/j.ymthe.2024.04.030","article-title":"Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma","volume":"32","author":"Xia","year":"2024","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1017\/S0007114511004260","article-title":"Lutein and zeaxanthin intake and the risk of age-related macular degeneration: A systematic review and meta-analysis","volume":"107","author":"Ma","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1001\/jamaophthalmol.2015.3590","article-title":"Intakes of Lutein, Zeaxanthin, and Other Carotenoids and Age-Related Macular Degeneration During 2 Decades of Prospective Follow-up","volume":"133","author":"Wu","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4103\/tcmj.tcmj_153_23","article-title":"Mediterranean diet as a modifiable risk factor for age-related macular degeneration: A systematic review and meta-analysis","volume":"36","author":"Angelia","year":"2024","journal-title":"Tzu Chi Med. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.ophtha.2024.12.005","article-title":"Omega-3 Fatty Acids as Protective Factors for Age-Related Macular Degeneration: Prospective Cohort and Mendelian Randomization Analyses","volume":"132","author":"Xue","year":"2025","journal-title":"Ophthalmology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3733\/ca.v065n03p106","article-title":"Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health","volume":"65","author":"Zivkovic","year":"2011","journal-title":"Calif. Agric."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1001\/jama.2017.1926","article-title":"Dietary Intake of Omega-3 Fatty Acids From Fish and Risk of Diabetic Retinopathy","volume":"317","author":"Chew","year":"2017","journal-title":"JAMA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1038\/s41433-025-03705-5","article-title":"Blood omega-3 biomarkers, diabetic retinopathy and retinal vessel status in patients with type 1 diabetes","volume":"39","author":"Vinagre","year":"2025","journal-title":"Eye"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1687","DOI":"10.1210\/clinem\/dgae482","article-title":"Fish Oil, Plasma n-3 PUFAs, and Risk of Macro- and Microvascular Complications Among Individuals With Type 2 Diabetes","volume":"110","author":"Tian","year":"2025","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.2147\/JIR.S306456","article-title":"Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT\/SIRT1\/NLRP3 Pathway","volume":"14","author":"Wan","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_73","first-page":"154768","article-title":"Therapeutic application of natural products: NAD(+) metabolism as potential target","volume":"114","author":"Guo","year":"2023","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Hewlings, S.J., and Kalman, D.S. (2017). Curcumin: A Review of Its Effects on Human Health. Foods, 6.","DOI":"10.3390\/foods6100092"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"181","DOI":"10.5114\/ceji.2019.87070","article-title":"Therapeutic potential of curcumin in eye diseases","volume":"44","author":"Hyc","year":"2019","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhang, L.X., Li, C.X., Kakar, M.U., Khan, M.S., Wu, P.F., Amir, R.M., Dai, D.F., Naveed, M., Li, Q.Y., and Saeed, M. (2021). Resveratrol (RV): A pharmacological review and call for further research. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112164"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e30786","DOI":"10.1016\/j.heliyon.2024.e30786","article-title":"Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway","volume":"10","author":"Yuan","year":"2024","journal-title":"Heliyon"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"117214","DOI":"10.1016\/j.taap.2024.117214","article-title":"Resveratrol alleviates reactive oxygen species and inflammation in diabetic retinopathy via SIRT1\/HMGB1 pathway-mediated ferroptosis","volume":"495","author":"Peng","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/S1734-1140(12)70948-9","article-title":"Resveratrol improves diabetic retinopathy possibly through oxidative stress\u2014Nuclear factor \u03baB\u2014Apoptosis pathway","volume":"64","author":"Soufi","year":"2012","journal-title":"Pharmacol. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Li, S., Gaur, U., Chong, C.M., Lin, S., Fang, J., Zeng, Z., Wang, H., and Zheng, W. (2018). Berberine Protects Human Retinal Pigment Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Damage through Activation of AMPK. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061736"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Hu, R.Y., Qi, S.M., Wang, Y.J., Li, W.L., Zou, W.C., Wang, Z., Ren, S., and Li, W. (2024). Ginsenoside Rg3 Improved Age-Related Macular Degeneration Through Inhibiting ROS-Mediated Mitochondrion-Dependent Apoptosis In Vivo and In Vitro. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111414"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Bian, M., Du, X., Wang, P., Cui, J., Xu, J., Gu, J., Zhang, T., and Chen, Y. (2017). Combination of ginsenoside Rb1 and Rd protects the retina against bright light-induced degeneration. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06471-x"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s11481-023-10073-y","article-title":"Ginsenoside Re Mitigates Photooxidative Stress-Mediated Photoreceptor Degeneration and Retinal Inflammation","volume":"18","author":"Chang","year":"2023","journal-title":"J. Neuroimmune Pharmacol. Off. J. Soc. NeuroImmune Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Lee, H., Nguyen Hoang, A.T., and Lee, S.J. (2022). Ginsenoside protopanaxadiol protects adult retinal pigment epithelial-19 cells from chloroquine by modulating autophagy and apoptosis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274763"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Yang, C.C., Chen, C.Y., Wu, C.C., Koo, M., Yu, Z.R., and Wang, B.J. (2016). Panax ginseng Fraction F3 Extracted by Supercritical Carbon Dioxide Protects against Oxidative Stress in ARPE-19 Cells. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101717"},{"key":"ref_86","first-page":"9420704","article-title":"Apigenin Protects Mouse Retina against Oxidative Damage by Regulating the Nrf2 Pathway and Autophagy","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1167\/tvst.9.6.8","article-title":"Apigenin and Ethaverine Hydrochloride Enhance Retinal Vascular Barrier In Vitro and In Vivo","volume":"9","author":"Jiang","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Li, P., Fang, R.L., Wang, W., Zeng, X.X., Lan, T., Liu, S.Y., Hu, Y.J., Shen, Q., Wang, S.W., and Tong, Y.H. (2024). Apigenin suppresses epithelial-mesenchymal transition in high glucose-induced retinal pigment epithelial cell by inhibiting CBP\/p300-mediated histone acetylation. Biochem. Biophys. Res. Commun., 717.","DOI":"10.1016\/j.bbrc.2024.150061"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Shoda, C., Lee, D., Miwa, Y., Yamagami, S., Nakashizuka, H., Nimura, K., Okamoto, K., Kawagishi, H., Negishi, K., and Kurihara, T. (2024). Inhibition of hypoxia-inducible factors suppresses subretinal fibrosis. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 38.","DOI":"10.1096\/fj.202400540RRR"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Liu, D., Zhang, C., Zhang, J., Xu, G.T., and Zhang, J. (2023). Molecular pathogenesis of subretinal fibrosis in neovascular AMD focusing on epithelial-mesenchymal transformation of retinal pigment epithelium. Neurobiol. Dis., 185.","DOI":"10.1016\/j.nbd.2023.106250"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/fft2.192","article-title":"Apigenin alleviates diabetic endothelial dysfunction through activating AMPK\/PI3K\/Akt\/eNOS and Nrf2\/HO-1 signaling pathways","volume":"4","author":"Miao","year":"2023","journal-title":"Food Front."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.exer.2010.03.016","article-title":"The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2\/Cx3cr1 double deficient mice","volume":"91","author":"Cao","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.4103\/1673-5374.301027","article-title":"Quercetin protects against diabetic retinopathy in rats by inducing heme oxygenase-1 expression","volume":"16","author":"Chai","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.nutres.2023.12.003","article-title":"Quercetin protects against hyperglycemia-induced retinopathy in Sprague Dawley rats by regulating the gut-retina axis and nuclear factor erythroid-2-related factor 2 pathway","volume":"122","author":"Liu","year":"2024","journal-title":"Nutr. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1016\/j.foodchem.2012.11.139","article-title":"A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention","volume":"138","author":"Chen","year":"2013","journal-title":"Food Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1089\/jop.2022.0128","article-title":"Kaempferol Protects Against Retinal Photoreceptor Degeneration in a Mouse Model of Light-Induced Retinal Injury","volume":"39","author":"Noguchi","year":"2023","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ibuki, M., Lee, D., Shinojima, A., Miwa, Y., Tsubota, K., and Kurihara, T. (2020). Rice Bran and Vitamin B6 Suppress Pathological Neovascularization in a Murine Model of Age-Related Macular Degeneration as Novel HIF Inhibitors. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238940"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S0006-8993(02)02587-8","article-title":"Vitamin B6 protects primate retinal neurons from ischemic injury","volume":"940","author":"Wang","year":"2002","journal-title":"Brain Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"D1516","DOI":"10.1093\/nar\/gkae1059","article-title":"PubChem 2025 update","volume":"53","author":"Kim","year":"2024","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/10923\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:00:05Z","timestamp":1762858805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/10923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":99,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262210923"],"URL":"https:\/\/doi.org\/10.3390\/ijms262210923","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]}}}