{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:55:33Z","timestamp":1789430133490,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council of the Republic of China","award":["NSTC112-2320-B-003-001"],"award-info":[{"award-number":["NSTC112-2320-B-003-001"]}]},{"name":"National Science and Technology Council of the Republic of China","award":["NSTC113-2320-B-003-002-MY3"],"award-info":[{"award-number":["NSTC113-2320-B-003-002-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Retinal degeneration is associated with dietary factors and environmental light exposure. This study investigated the effects of a high-fructose high-fat (HFHF) diet on susceptibility to blue light (BL)-induced retinal damage. Male ICR mice were randomized into three groups: control, BL alone, and BL plus HFHF diet (BL + HFHF). The BL + HFHF group consumed the HFHF diet for 40 weeks, followed by 8 weeks of low-intensity BL exposure (465 nm, 37.7 lux, 0.8 \u03bcW\/cm2) for 6 h daily. The BL group underwent the same BL exposure while kept on a standard diet. Histopathological analysis showed that, under BL exposure, the HFHF diet significantly reduced the number of photoreceptor nuclei and the thickness of the outer nuclear layer and inner\/outer segments compared to the BL group (p &lt; 0.05). While BL exposure alone caused oxidative DNA damage, rhodopsin loss, and M\u00fcller cell activation, the combination with an HFHF diet significantly amplified the oxidative DNA damage and M\u00fcller cell activation. Moreover, the HFHF diet increased blood\u2013retinal barrier permeability and triggered apoptosis under BL exposure. Mechanistically, the BL + HFHF group exhibited increased retinal advanced glycated end product (AGE) deposition, accompanied by the activation of the receptor for AGE (RAGE), NF\u03baB, and the NLRP3 inflammasome-dependent IL-1\u03b2 pathway. In conclusion, this study underscores that unhealthy dietary factors, particularly those high in fructose and fat, may intensify the hazard of BL and adversely impact visual health.<\/jats:p>","DOI":"10.3390\/antiox14080898","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T15:00:42Z","timestamp":1753196442000},"page":"898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High-Fructose High-Fat Diet Renders the Retina More Susceptible to Blue Light Photodamage in Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Meng-Wei","family":"Kao","sequence":"first","affiliation":[{"name":"Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0723-3002","authenticated-orcid":false,"given":"Wan-Ju","family":"Yeh","sequence":"additional","affiliation":[{"name":"Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7243-3436","authenticated-orcid":false,"given":"Chi-Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","unstructured":"Kepios Pte. Ltd. (2023). Digital 2023 Global Digital Overview, Kepios Pte. Ltd."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101452","DOI":"10.1016\/j.eclinm.2022.101452","article-title":"Changes and correlates of screen time in adults and children during the COVID-19 pandemic: A systematic review and meta-analysis","volume":"48","author":"Trott","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110142","DOI":"10.1016\/j.exer.2024.110142","article-title":"A comprehensive review of experimental models for investigating blue light-induced ocular damage: Insights into parameters, limitations, and new opportunities","volume":"249","author":"Yeh","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1985","DOI":"10.1038\/cddis.2015.333","article-title":"Blue light-induced retinal lesions, intraretinal vascular leakage and edema formation in the all-cone mouse retina","volume":"6","author":"Geiger","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1289\/ehp.1307294","article-title":"White light\u2013emitting diodes (LEDs) at domestic lighting levels and retinal injury in a rat model","volume":"122","author":"Shang","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6435364","DOI":"10.1155\/2019\/6435364","article-title":"Mitochondria as potential targets and initiators of the blue light hazard to the retina","volume":"2019","author":"Tao","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Li, H., Zhang, M., Wang, D., Dong, G., Chen, Z., Li, S., Sun, X., Zeng, M., Liao, H., and Chen, H. (2021). Blue light from cell phones can cause chronic retinal light injury: The evidence from a clinical observational study and a SD rat model. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/3236892"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zi\u00f3\u0142kowska, N., Lewczuk, B., Szyry\u0144ska, N., Rawicka, A., and Vyniarska, A. (2023). Low-intensity blue light exposure reduces melanopsin expression in intrinsically photosensitive retinal ganglion cells and damages mitochondria in retinal ganglion cells in Wistar rats. Cells, 12.","DOI":"10.3390\/cells12071014"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Rinninella, E., Mele, M.C., Merendino, N., Cintoni, M., Anselmi, G., Caporossi, A., Gasbarrini, A., and Minnella, A.M. (2018). The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut\u2013Retina Axis. Nutrients, 10.","DOI":"10.20944\/preprints201810.0369.v1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108440","DOI":"10.1016\/j.exer.2021.108440","article-title":"Impacts of high fat diet on ocular outcomes in rodent models of visual disease","volume":"204","author":"Douglass","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.preteyeres.2017.11.002","article-title":"Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism","volume":"64","author":"Joyal","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Malesza, I.J., Malesza, M., Walkowiak, J., Mussin, N., Walkowiak, D., Aringazina, R., Bartkowiak-Wieczorek, J., and M\u0105dry, E. (2021). High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells, 10.","DOI":"10.3390\/cells10113164"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"bqz006","DOI":"10.1210\/endocr\/bqz006","article-title":"Advanced glycation end products: Building on the concept of the \u201ccommon soil\u201d in metabolic disease","volume":"161","author":"Ruiz","year":"2020","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Aimaretti, E., Chimienti, G., Rubeo, C., Di Lorenzo, R., Trisolini, L., Bello, F.D., Moradi, A., Collino, M., Lezza, A.M.S., and Aragno, M. (2023). Different effects of high-fat\/high-sucrose and high-fructose diets on advanced glycation end-product accumulation and on mitochondrial involvement in heart and skeletal muscle in mice. Nutrients, 15.","DOI":"10.3390\/nu15234874"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1093\/ajcn\/86.1.180","article-title":"Association between dietary glycemic index and age-related macular degeneration in nondiabetic participants in the Age-Related Eye Disease Study","volume":"86","author":"Chiu","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Varoniukaite, A., Verkauskiene, R., Simoniene, D., Paskeviciene, D., and Balciuniene, V. (2025). Advanced glycation end products association with diabetic retinopathy severity. Acta Ophthalmol., 103.","DOI":"10.1111\/aos.17405"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, Z., Tu, C., Chen, X., and He, R. (2025). Advanced Glycation End Products in Disease Development and Potential Interventions. Antioxidants, 14.","DOI":"10.3390\/antiox14040492"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1021\/acs.jafc.7b05943","article-title":"Perspective of advanced glycation end products on human health","volume":"66","author":"Lin","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shen, C.Y., Lu, C.H., Wu, C.H., Li, K.J., Kuo, Y.M., Hsieh, S.C., and Yu, C.L. (2020). The Development of Maillard Reaction, and Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling Inhibitors as Novel Therapeutic Strategies for Patients with AGE-Related Diseases. Molecules, 25.","DOI":"10.3390\/molecules25235591"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/ceo.13343","article-title":"Role of diet and food intake in age-related macular degeneration: A systematic review","volume":"47","author":"Chapman","year":"2019","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sbai, O., Torrisi, F., Fabrizio, F.P., Rabbeni, G., and Perrone, L. (2024). Effect of the mediterranean diet (MeDi) on the progression of retinal disease: A narrative review. Nutrients, 16.","DOI":"10.3390\/nu16183169"},{"key":"ref_22","first-page":"664","article-title":"Biological and clinical significance of the AGE-RAGE axis in the aggressiveness and prognosis of prostate cancer","volume":"31","author":"Khoo","year":"2023","journal-title":"J. Food Drug Anal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/aos.15226","article-title":"Lipid metabolism and retinal diseases","volume":"100","author":"Gabrielle","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yan, Y., Wu, Y., Zhao, Y., Yang, Y., An, G., Liu, Z., and Qi, D. (2025). A review on eye diseases induced by blue light: Pathology, model, active ingredients and mechanisms. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1513406"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s40123-023-00675-3","article-title":"Blue Light Exposure: Ocular Hazards and Prevention-A Narrative Review","volume":"12","author":"Merle","year":"2023","journal-title":"Ophthalmol. Ther."},{"key":"ref_26","first-page":"191","article-title":"Light-emitting-diode induced retinal damage and its wavelength dependency in vivo","volume":"10","author":"Shang","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2468","DOI":"10.1038\/cddis.2016.363","article-title":"Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light","volume":"7","author":"Hu","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"61","DOI":"10.63500\/mv_v22_61","article-title":"Effects of blue light on the circadian system and eye physiology","volume":"22","author":"Tosini","year":"2016","journal-title":"Mol. Vis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/annweh\/wxy110","article-title":"Light exposure during days with night, outdoor, and indoor work","volume":"63","author":"Daugaard","year":"2019","journal-title":"Ann. Work Expo. Health"},{"key":"ref_30","first-page":"1614","article-title":"Photoreceptor damage induced by low-intensity light: Model of retinal degeneration in mammals","volume":"19","author":"Arietti","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.2147\/DDDT.S176349","article-title":"17\u03b2-estradiol ameliorates oxidative stress and blue light-emitting diode-induced retinal degeneration by decreasing apoptosis and enhancing autophagy","volume":"12","author":"Wei","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10654-017-0338-8","article-title":"Diet and risk of diabetic retinopathy: A systematic review","volume":"33","author":"Dow","year":"2018","journal-title":"Eur. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1007\/s12011-020-02526-9","article-title":"Different Sources of Dietary Magnesium Supplementation Reduces Oxidative Stress by Regulation Nrf2 and NF-\u03baB Signaling Pathways in High-Fat Diet Rats","volume":"199","author":"Orhan","year":"2021","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"108059","DOI":"10.1016\/j.exer.2020.108059","article-title":"Impact of a high-fat diet on the fatty acid composition of the retina","volume":"196","author":"Albouery","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2100823","DOI":"10.1002\/mnfr.202100823","article-title":"A High Fat \u201cWestern-style\u201d Diet Induces AMD-Like Features in Wildtype Mice","volume":"66","author":"Keeling","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1167\/iovs.14-16143","article-title":"High-fat diet\u2013induced retinal dysfunction","volume":"56","author":"Chang","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1021\/acs.chemrestox.1c00221","article-title":"Diet and Obesity-Induced Methylglyoxal Production and Links to Metabolic Disease","volume":"34","author":"Shuck","year":"2021","journal-title":"Chem. Res. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.freeradbiomed.2015.12.022","article-title":"Fructose-derived advanced glycation end-products drive lipogenesis and skeletal muscle reprogramming via SREBP-1c dysregulation in mice","volume":"91","author":"Mastrocola","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E4472","DOI":"10.1073\/pnas.1702302114","article-title":"Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration","volume":"114","author":"Rowan","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2100122118","DOI":"10.1073\/pnas.2100122118","article-title":"Lipofuscin causes atypical necroptosis through lysosomal membrane permeabilization","volume":"118","author":"Pan","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/febs.16330","article-title":"The blood-retina barrier in health and disease","volume":"290","author":"Campbell","year":"2023","journal-title":"FEBS J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1861940","DOI":"10.1155\/2022\/1861940","article-title":"GLP-1 RA Improves Diabetic Retinopathy by Protecting the Blood-Retinal Barrier through GLP-1R-ROCK-p-MLC Signaling Pathway","volume":"2022","author":"Wei","year":"2022","journal-title":"J. Diabetes Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12987-023-00430-7","article-title":"Blue light exposure collapses the inner blood-retinal barrier by accelerating endothelial CLDN5 degradation through the disturbance of GNAZ and the activation of ADAM17","volume":"20","author":"Chan","year":"2023","journal-title":"Fluids Barriers CNS"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.2337\/db15-1255","article-title":"Functional Deficits Precede Structural Lesions in Mice with High-Fat Diet-Induced Diabetic Retinopathy","volume":"65","author":"Rajagopal","year":"2016","journal-title":"Diabetes"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/8\/898\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:14:05Z","timestamp":1760033645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/8\/898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":44,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["antiox14080898"],"URL":"https:\/\/doi.org\/10.3390\/antiox14080898","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]}}}