{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:50:18Z","timestamp":1787064618961,"version":"build-2736575974"},"reference-count":91,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total\u00ae; N) on oxidative stress and inflammation-like induced conditions by H2O2 and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H2O2-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFN\u03b3 in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total\u00ae protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.<\/jats:p>","DOI":"10.3390\/nu13051423","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T21:49:20Z","timestamp":1619300960000},"page":"1423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"13","author":[{"given":"Maria","family":"Hernandez","sequence":"first","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa Sanitaria en Enfermedades Oculares (Oftared), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-9725","authenticated-orcid":false,"given":"Sergio","family":"Recalde","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa Sanitaria en Enfermedades Oculares (Oftared), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gonz\u00e1lez-Zamora","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Bilbao-Malav\u00e9","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-4535","authenticated-orcid":false,"given":"Manuel","family":"S\u00e1enz de Viteri","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa Sanitaria en Enfermedades 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Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0654-0249","authenticated-orcid":false,"given":"Jes\u00fas","family":"Barrio-Barrio","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa Sanitaria en Enfermedades Oculares (Oftared), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Fernandez-Robredo","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa Sanitaria en Enfermedades Oculares (Oftared), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Garc\u00eda-Layana","sequence":"additional","affiliation":[{"name":"Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research, IdiSNA, 31008 Pamplona, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa Sanitaria en Enfermedades Oculares (Oftared), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","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_2","first-page":"74","article-title":"Age-related macular degeneration","volume":"59","author":"Gheorghe","year":"2015","journal-title":"Rom. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","article-title":"Age-related macular degeneration","volume":"392","author":"Mitchell","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1001\/archophthalmol.2010.92","article-title":"The prevalence of age-related macular degeneration and associated risk factors","volume":"128","author":"Klein","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.ophtha.2012.10.036","article-title":"Clinical classification of age-related macular degeneration","volume":"120","author":"Ferris","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1001\/archopht.1992.01080130101035","article-title":"The long-term effects of visible light on the eye","volume":"110","author":"Taylor","year":"1992","journal-title":"Arch. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1001\/archopht.120.10.1357","article-title":"Smoking and the 5-year incidence of age-related maculopathy: The Blue Mountains Eye Study","volume":"120","author":"Mitchell","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ajo.2003.11.069","article-title":"The epidemiology of age-related macular degeneration","volume":"137","author":"Klein","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1001\/archopht.1994.01090190080025","article-title":"Heredity and age-related macular degeneration. Observations in monozygotic twins","volume":"112","author":"Klein","year":"1994","journal-title":"Arch. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1001\/archopht.1995.01100060069034","article-title":"Dietary fat and age-related maculopathy","volume":"113","author":"Brady","year":"1995","journal-title":"Arch. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"518s","DOI":"10.1093\/jn\/132.3.518S","article-title":"The body of evidence to support a protective role for lutein and zeaxanthin in delaying chronic disease. Overview","volume":"132","author":"Millen","year":"2002","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mares, J. (2004). Carotenoids and eye disease: Epidemiological evidence. Krinsky NI Mayne ST Sies Heds. Carotenoids in Health and Disease, Marcel Dekker Inc.","DOI":"10.1201\/9780203026649.ch19"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1001\/archopht.119.8.1191","article-title":"Dietary fat and risk for advanced age-related macular degeneration","volume":"119","author":"Seddon","year":"2001","journal-title":"Arch. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration","volume":"45","author":"Beatty","year":"2000","journal-title":"Surv. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1017\/S146239941000164X","article-title":"Oxidation and age-related macular degeneration: Insights from molecular biology","volume":"12","author":"Khandhadia","year":"2010","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Layana, A.G., Minnella, A.M., Garh\u00f6fer, G., Aslam, T., Holz, F.G., Leys, A., Silva, R., Delcourt, C., Souied, E., and Seddon, J.M. (2017). Vitamin D and Age-Related Macular Degeneration. Nutrients, 9.","DOI":"10.3390\/nu9101120"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alizadeh, E., Mammadzada, P., and Andr\u00e9, H. (2018). The Different Facades of Retinal and Choroidal Endothelial Cells in Response to Hypoxia. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123846"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nrclinonc.2009.64","article-title":"Branching morphogenesis and antiangiogenesis candidates: Tip cells lead the way","volume":"6","author":"Carmeliet","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"(2001). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch. Ophthalmol., 119, 1417\u20131436.","DOI":"10.1001\/archopht.119.10.1417"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"(2013). Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA, 309, 2005\u20132015.","DOI":"10.1001\/jama.2013.4997"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1001\/archopht.125.5.661","article-title":"Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994","volume":"125","author":"Parekh","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1167\/iovs.06-1210","article-title":"Calcitriol is a potent inhibitor of retinal neovascularization","volume":"48","author":"Albert","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.maturitas.2016.04.002","article-title":"Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis","volume":"88","author":"Annweiler","year":"2016","journal-title":"Maturitas"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1167\/iovs.17-21673","article-title":"Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration","volume":"58","author":"Merle","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.5001\/omj.2020.01","article-title":"The Possible Link Between Vitamin D Levels and Exudative Age-related Macular Degeneration","volume":"35","author":"Kan","year":"2020","journal-title":"Oman. Med. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1167\/iovs.18-25945","article-title":"Serum 25-Hydroxyvitamin D Concentrations and Incidence of Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study","volume":"60","author":"Millen","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1007\/s12603-016-0827-6","article-title":"Vitamin D Status and Prevalent Early Age-Related Macular Degeneration in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"21","author":"Millen","year":"2017","journal-title":"J. Nutr. Health Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20723","DOI":"10.1038\/srep20723","article-title":"Dietary n-3 Fatty Acid, \u03b1-Tocopherol, Zinc, vitamin D, vitamin C, and \u03b2-carotene are Associated with Age-Related Macular Degeneration in Japan","volume":"6","author":"Aoki","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33083","DOI":"10.1038\/srep33083","article-title":"Vitamin D Supplementation for Patients with Dry Eye Syndrome Refractory to Conventional Treatment","volume":"6","author":"Bae","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"312","DOI":"10.5935\/0004-2749.20200043","article-title":"Clinical outcomes of ocular surface in patients treated with vitamin D oral replacement","volume":"83","author":"Karaca","year":"2020","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1167\/iovs.13-13019","article-title":"Characterization of vitamin D production by human ocular barrier cells","volume":"55","author":"Alsalem","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.exer.2015.02.019","article-title":"Vitamin D: Implications for ocular disease and therapeutic potential","volume":"134","author":"Reins","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1210\/me.2010-0392","article-title":"Research resource: Nuclear receptor atlas of human retinal pigment epithelial cells: Potential relevance to age-related macular degeneration","volume":"25","author":"Dwyer","year":"2011","journal-title":"Mol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"H753","DOI":"10.1152\/ajpheart.00319.2017","article-title":"Vitamin D and regulation of vascular cell function","volume":"314","author":"Jamali","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tohari, A.M., Alhasani, R.H., Biswas, L., Patnaik, S.R., Reilly, J., Zeng, Z., and Shu, X. (2019). Vitamin D Attenuates Oxidative Damage and Inflammation in Retinal Pigment Epithelial Cells. Antioxidants, 8.","DOI":"10.3390\/antiox8090341"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fernandez-Robredo, P., Gonz\u00e1lez-Zamora, J., Recalde, S., Bilbao-Malav\u00e9, V., Bezunartea, J., Hernandez, M., and Garcia-Layana, A. (2020). Vitamin D Protects against Oxidative Stress and Inflammation in Human Retinal Cells. Antioxidants, 9.","DOI":"10.3390\/antiox9090838"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3109\/02713689508999921","article-title":"Immuno-localization of the calcitriol receptor, calbindin-D28k and the plasma membrane calcium pump in the human eye","volume":"14","author":"Johnson","year":"1995","journal-title":"Curr. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1186\/1479-7364-5-6-538","article-title":"Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration","volume":"5","author":"Morrison","year":"2011","journal-title":"Hum. Genom."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1001\/archophthalmol.2011.48","article-title":"Vitamin D status and early age-related macular degeneration in postmenopausal women","volume":"129","author":"Millen","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/eye.2011.174","article-title":"Reconsidering the connection between vitamin D levels and age-related macular degeneration","volume":"25","author":"Golan","year":"2011","journal-title":"Eye (London)"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1001\/archophthalmol.2012.439","article-title":"Association of vitamin D deficiency and age-related macular degeneration in medicare beneficiaries","volume":"130","author":"Day","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.3945\/jn.115.214387","article-title":"Vitamin D Deficiency in Community-Dwelling Elderly Is Not Associated with Age-Related Macular Degeneration","volume":"145","author":"Merle","year":"2015","journal-title":"J. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1167\/iovs.14-14763","article-title":"Inverse relationship between high blood 25-hydroxyvitamin D and late stage of age-related macular degeneration in a representative Korean population","volume":"55","author":"Kim","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1167\/iovs.03-0351","article-title":"Oxidative stress affects the junctional integrity of retinal pigment epithelial cells","volume":"45","author":"Bailey","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","first-page":"1594","article-title":"Protection of tight junction between RPE cells with tissue factor targeting peptide","volume":"11","author":"Zou","year":"2018","journal-title":"Int. J. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1167\/iovs.61.2.4","article-title":"Vitamin-D3 (\u03b1-1, 25(OH) 2D3) Protects Retinal Pigment Epithelium From Hyperoxic Insults","volume":"61","author":"Murugeswari","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1083\/jcb.129.2.507","article-title":"Plasticity in epithelial cell phenotype: Modulation by expression of different cadherin cell adhesion molecules","volume":"129","author":"Marrs","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/10590500902885684","article-title":"8-hydroxy-2\u2032-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis","volume":"27","author":"Valavanidis","year":"2009","journal-title":"J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.3109\/02713680903353772","article-title":"Oxidative macromolecular damage in age-related macular degeneration","volume":"34","author":"Totan","year":"2009","journal-title":"Curr. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7901270","DOI":"10.1155\/2020\/7901270","article-title":"Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models","volume":"2020","author":"Abokyi","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ma, Z., Liu, J., Li, J., Jiang, H., and Kong, J. (2020). Klotho Levels are Decreased and Associated with Enhanced Oxidative Stress and Inflammation in the Aqueous Humor in Patients with Exudative Age-related Macular Degeneration. Ocul. Immunol. Inflamm., 1\u20138.","DOI":"10.1080\/09273948.2020.1828488"},{"key":"ref_52","first-page":"293","article-title":"Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: A new phenotype in Central Africa?","volume":"7","author":"Masamba","year":"2014","journal-title":"Int. J. Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wang, W., and Lo, A.C.Y. (2018). Diabetic Retinopathy: Pathophysiology and Treatments. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061816"},{"key":"ref_54","first-page":"138","article-title":"Effects of Vitamin D supplementation on 8-hydroxydeoxy guanosine and 3-nitrotyrosine in patients with type 2 diabetes: A randomized clinical trial","volume":"21","author":"Damghanian","year":"2019","journal-title":"Prog. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/cbf.3167","article-title":"Protection against oxidative stress by vitamin D in cone cells","volume":"34","author":"Tohari","year":"2016","journal-title":"Cell Biochem. Funct."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1016\/j.bbamcr.2016.09.012","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","year":"2016","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3179s","DOI":"10.1093\/jn\/134.11.3179S","article-title":"Antioxidants suppress apoptosis","volume":"134","author":"Zeisel","year":"2004","journal-title":"J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1076\/ceyr.22.3.165.5517","article-title":"Hydrogen peroxide stimulates apoptosis in cultured human retinal pigment epithelial cells","volume":"22","author":"Jin","year":"2001","journal-title":"Curr. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1007\/s10495-012-0750-1","article-title":"Enhanced apoptosis in retinal pigment epithelium under inflammatory stimuli and oxidative stress","volume":"17","author":"Wang","year":"2012","journal-title":"Apoptosis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"112023","DOI":"10.1016\/j.yexcr.2020.112023","article-title":"Protection by vitamin D against high-glucose-induced damage in retinal pigment epithelial cells","volume":"392","author":"Tohari","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8193523","DOI":"10.1155\/2018\/8193523","article-title":"Vitamin D(3) Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS\/TXNIP\/NLRP3 Inflammasome Pathway","volume":"2018","author":"Lu","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1908164","DOI":"10.1155\/2016\/1908164","article-title":"Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications","volume":"2016","author":"Arroyo","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2174\/1874205X01610010083","article-title":"Oxidative Stress Induces Senescence in Cultured RPE Cells","volume":"10","author":"Aryan","year":"2016","journal-title":"Open Neurol. J."},{"key":"ref_64","first-page":"507","article-title":"Oxidative stress affects retinal pigment epithelial cell survival through epidermal growth factor receptor\/AKT signaling pathway","volume":"10","author":"Chen","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Blasiak, J., Barszczewska, G., Gralewska, P., and Kaarniranta, K. (2019). Oxidative stress induces mitochondrial dysfunction and autophagy in ARPE-19 cells. Acta. Ophthalmol., 97.","DOI":"10.1111\/j.1755-3768.2019.5425"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.redox.2017.04.039","article-title":"Quantitative biology of hydrogen peroxide signaling","volume":"13","author":"Antunes","year":"2017","journal-title":"Redox Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1089\/ars.2009.2728","article-title":"Hydrogen peroxide as a cell-survival signaling molecule","volume":"11","author":"Groeger","year":"2009","journal-title":"Antioxid Redox Signal"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.redox.2014.02.006","article-title":"Hydrogen peroxide sensing, signaling and regulation of transcription factors","volume":"2","author":"Marinho","year":"2014","journal-title":"Redox Biol."},{"key":"ref_69","first-page":"2292","article-title":"Effect of TNF-alpha on human ARPE-19-secreted proteins","volume":"14","author":"An","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_70","first-page":"1156","article-title":"Proinflammatory cytokines decrease the expression of genes critical for RPE function","volume":"22","author":"Kutty","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhao, M., Bai, Y., Xie, W., Shi, X., Li, F., Yang, F., Sun, Y., Huang, L., and Li, X. (2015). Interleukin-1\u03b2 Level Is Increased in Vitreous of Patients with Neovascular Age-Related Macular Degeneration (nAMD) and Polypoidal Choroidal Vasculopathy (PCV). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125150"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3389\/fimmu.2019.01618","article-title":"IL-1 Family Members Mediate Cell Death, Inflammation and Angiogenesis in Retinal Degenerative Diseases","volume":"10","author":"Wooff","year":"2019","journal-title":"Front Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1136\/bjo.2007.123190","article-title":"Interleukin-8 promoter polymorphism -251A\/T is a risk factor for age-related macular degeneration","volume":"92","author":"Goverdhan","year":"2008","journal-title":"Br J. Ophthalmol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijge.2012.01.018","article-title":"Choroidal Neovascular Membrane in Age-Related Macular Degeneration is Associated with Increased Interleukin-6","volume":"6","author":"Yildirim","year":"2012","journal-title":"Int. J. Gerontol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/s00417-014-2738-8","article-title":"Serum cytokines as biomarkers for age-related macular degeneration","volume":"253","author":"Nassar","year":"2015","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1167\/iovs.18-25878","article-title":"Systemic Levels of Interleukin-6 Correlate With Progression Rate of Geographic Atrophy Secondary to Age-Related Macular Degeneration","volume":"60","author":"Subhi","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Klettner, A., and Dithmar, S. (2020). The RPE Cell and the Immune System. Retinal Pigment Epithelium in Health and Disease, Springer.","DOI":"10.1007\/978-3-030-28384-1"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"582842","DOI":"10.1155\/2014\/582842","article-title":"Age-related macular degeneration: Insights into inflammatory genes","volume":"2014","author":"Cascella","year":"2014","journal-title":"J. Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ecl.2010.02.010","article-title":"Vitamin D and the immune system: New perspectives on an old theme","volume":"39","author":"Hewison","year":"2010","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.jbspin.2010.09.018","article-title":"Vitamin D and inflammation","volume":"77","author":"Guillot","year":"2010","journal-title":"Joint Bone Spine"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nm.2717","article-title":"NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components","volume":"18","author":"Doyle","year":"2012","journal-title":"Nat. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/eye.2017.241","article-title":"Inflammasomes, the eye and anti-inflammasome therapy","volume":"32","author":"Yerramothu","year":"2018","journal-title":"Eye (London)"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2174\/187152809787582507","article-title":"The IL-12 family of cytokines in infection, inflammation and autoimmune disorders","volume":"8","author":"Gee","year":"2009","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.cell.2010.01.040","article-title":"The inflammasomes","volume":"140","author":"Schroder","year":"2010","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sommer, A., and Fabri, M. (2015). Vitamin D regulates cytokine patterns secreted by dendritic cells to promote differentiation of IL-22-producing T cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130395"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"881","DOI":"10.2310\/JIM.0b013e31821b8755","article-title":"Vitamin D and the immune system","volume":"59","author":"Aranow","year":"2011","journal-title":"J. Investig. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1530\/eje.0.1450351","article-title":"1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes","volume":"145","author":"Canning","year":"2001","journal-title":"Eur. J. Endocrinol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lightman, S., and Calder, V. (2006). Is IL-10 a good target to inhibit choroidal neovascularisation in age-related macular disease?. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030364"},{"key":"ref_89","first-page":"7301","article-title":"IL-10 inhibits retinal pigment epithelium cell proliferation and migration through regulation of VEGF in rhegmatogenous retinal detachment","volume":"17","author":"Zhao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/path.4816","article-title":"Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye","volume":"241","author":"Theodoropoulou","year":"2017","journal-title":"J. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1002\/eji.201444671","article-title":"IL-33 attenuates the development of experimental autoimmune uveitis","volume":"44","author":"Barbour","year":"2014","journal-title":"Eur. J. Immunol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/5\/1423\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:52:00Z","timestamp":1760161920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/5\/1423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":91,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["nu13051423"],"URL":"https:\/\/doi.org\/10.3390\/nu13051423","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]}}}