180+
Peer-Reviewed Studies
13
Chapters
40+
Years of Research
Jump to Chapter
Chapter 1: Introduction
- Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040. Lancet Glob Health. 2014;2(2):e106-116. PMID: 25104651
- Rein DB, Wittenborn JS, Burke-Conte Z, et al. Prevalence of Age-Related Macular Degeneration in the US in 2019. JAMA Ophthalmol. 2022;140(12):1202-1208. PMID: 36326752
Chapter 2: Understanding Macular Degeneration
- Wong WL, Su X, Li X, et al. Global prevalence of AMD and disease burden projection. Lancet Glob Health. 2014;2(2):e106-116. PMID: 25104651
- Ferris FL 3rd, Wilkinson CP, Bird A, et al. Clinical Classification of Age-related Macular Degeneration. Ophthalmology. 2013;120(4):844-851. PMID: 23332590
- Bergen AA, Arya S, Koster C, et al. On the origin of proteins in human drusen. Prog Retin Eye Res. 2019;70:55-84. PMID: 30572124
- Curcio CA, Millican CL, Bailey T, Kruth HS. Accumulation of cholesterol with age in human Bruch's membrane. Invest Ophthalmol Vis Sci. 2001;42(1):265-274. PMID: 11133878
- Crabb JW, Miyagi M, Gu X, et al. Drusen proteome analysis. Proc Natl Acad Sci U S A. 2002;99(23):14682-14687. PMID: 12391305
- Hurley JB, Lindsay KJ, Du J. Glucose, lactate, and shuttling of metabolites in vertebrate retinas. J Neurosci Res. 2015;93(7):1079-1092. PMID: 25801286
- Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res. 2003;22(1):1-29. PMID: 12597922
- Campochiaro PA. Molecular pathogenesis of retinal and choroidal vascular diseases. Prog Retin Eye Res. 2015;49:67-81. PMID: 26113212
- Fleckenstein M, Keenan TDL, Guymer RH, et al. Age-related macular degeneration. Nat Rev Dis Primers. 2021;7(1):31. PMID: 33958600
- Hollyfield JG, Bonilha VL, Rayborn ME, et al. Oxidative damage-induced inflammation initiates AMD. Nat Med. 2008;14(2):194-198. PMID: 18223656
- Cho E, Hung S, Willett WC, et al. Prospective study of dietary fat and AMD risk. Am J Clin Nutr. 2001;73(2):209-218. PMID: 11157315
- Chong EW, et al. Dietary omega-3 and fish intake in AMD prevention. Arch Ophthalmol. 2008;126(6):826-33. PMID: 18541848
- Nakamura M, Kuse Y, Tsuruma K, et al. Oxidative Stress in Blue LED Light-Induced Retinal Damage. Biol Pharm Bull. 2017;40(8):1219-1225. PMID: 28769003
- Boyer DS, Hu A, Warrow D, et al. LIGHTSITE III: Photobiomodulation in Dry AMD. Retina. 2024;44(3):487-497. PMID: 38227884
- Saini JS, Corneo B, Miller JD, et al. Nicotinamide Ameliorates Disease Phenotypes in AMD iPSC Model. Cell Stem Cell. 2017;20(5):635-647. PMID: 28132833
- Keszler A, et al. Red/NIR light stimulates vasodilator release in diabetes. Free Radic Biol Med. 2017;113:157-164. PMID: 28927764
- Richer S, Stiles W, Ulanski L, et al. Resveratrol-based nutritional supplement in octogenarians with AMD. Nutrients. 2013;5(6):1989-2005. PMID: 23736827
- Beatty S, Koh H, Henson D, Boulton M. Role of oxidative stress in AMD pathogenesis. Surv Ophthalmol. 2000;45(2):115-134. PMID: 11033038
- Gu X, Meer SG, Miyagi M, et al. Carboxyethylpyrrole protein adducts as AMD biomarkers. J Biol Chem. 2003;278(43):42027-42035. PMID: 12923198
- Du J, Rountree A, Bhagat A, et al. Photoreceptor cells are major consumers of glucose. Am J Physiol Cell Physiol. 2016;311(1):C115-C125. PMID: 27167178
Chapter 3: The Root Cause
- Geiser F, Kenagy GJ. Polyunsaturated lipid diet lengthens torpor in hibernator. Am J Physiol. 1987;252(5 Pt 2):R897-901. PMID: 3578556
- Ruf T, Arnold W. Effects of PUFAs on hibernation and torpor. Am J Physiol Regul Integr Comp Physiol. 2008;294(3):R1044-52. PMID: 18171691
- Gerson AR, et al. Role of PUFAs in mitochondrial function during hibernation. J Exp Biol. 2008;211(16):2689-99. PMID: 18689422
- Blasbalg TL, Hibbeln JR, Ramsden CE, et al. Changes in omega-3 and omega-6 consumption during 20th century. Am J Clin Nutr. 2011;93(5):950-962. PMID: 21367944
- Hibbeln JR, et al. Healthy intakes of n-3 and n-6 fatty acids. Am J Clin Nutr. 2006;83(6):1483S-1493S. PMID: 16841858
- Simopoulos AP. Importance of omega-6/omega-3 ratio in cardiovascular disease. Exp Biol Med. 2008;233(6):674-88. PMID: 18408140
- Seddon JM, Cote J, Rosner B. AMD progression and dietary fat. Arch Ophthalmol. 2003;121(12):1728-1737. PMID: 14662593
- Knobbe CA, Stojanoska M. Displacing Foods of Modern Commerce as primary cause of AMD. Med Hypotheses. 2017;109:184-198. PMID: 29150279
- Tanito M, Elliott MH, et al. Protein modifications by 4-HNE in light-exposed rat retina. Invest Ophthalmol Vis Sci. 2005;46(10):3859-3868. PMID: 16186375
- Kendrick M. The Clot Thickens: The Enduring Mystery of Heart Disease. Columbus Publishing Ltd; 2021.
- Nieuwdorp M, et al. Loss of endothelial glycocalyx during acute hyperglycemia. Diabetes. 2006;55(2):480-486. PMID: 16443784
- Yoo K, et al. Chronic Stress and AMD in All of Us Research Program. Am J Ophthalmol. 2025;272:150-160. PMID: 39894426
- Seddon JM, et al. C-reactive protein and AMD. JAMA. 2004;291(6):704-710. PMID: 14871913
- Thornton J, et al. Smoking and AMD: a review. Eye. 2005;19(9):935-944. PMID: 15803172
Chapter 4: DHA, Light, and the Paradox of Protection
- Crawford MA, Bloom M, Broadhurst CL, et al. Evidence for the unique function of docosahexaenoic acid during the evolution of the modern hominid brain. Lipids. 1999;34 Suppl:S39-47. PMID: 10419087
- Marean CW, Bar-Matthews M, Bernatchez J, et al. Early human use of marine resources and pigment in South Africa during the Middle Pleistocene. Nature. 2007;449(7164):905-908. PMID: 17943129
- Cunnane SC, Crawford MA. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution. J Hum Evol. 2014;77:88-98. PMID: 24928072
- Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG. Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci U S A. 2004;101(22):8491-8496. PMID: 15152078
- Shindou H, Koso H, Sasaki J, et al. Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells. J Biol Chem. 2017;292(29):12054-12064. PMID: 28578316
- Blasbalg TL, Hibbeln JR, Ramsden CE, et al. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011;93(5):950-962. PMID: 21367944
- Bazan NG. Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain Pathol. 2005;15(2):159-166. PMID: 15912889
- Cho E, Hung S, Willett WC, et al. Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr. 2001;73(2):209-218. PMID: 11157315
- Chong EW, et al. Dietary omega-3 fatty acid and fish intake in the primary prevention of AMD. Arch Ophthalmol. 2008;126(6):826-833. PMID: 18541848
- Hamblin MR. Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation. Photochem Photobiol. 2018;94(2):199-212. PMID: 29164625
Chapter 5: Restoring Mitochondrial Function
- Hamblin MR. Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation. Photochem Photobiol. 2018;94(2):199-212. PMID: 29164625
- Keszler A, et al. Red/NIR light stimulates vasodilator release. Free Radic Biol Med. 2017;113:157-164. PMID: 28927764
- Powner MB, et al. Light stimulation of mitochondria reduces blood glucose. J Biophotonics. 2024;17(5):e202300521. PMID: 38378043
- Boyer DS, et al. LIGHTSITE III: PBM in Dry AMD. Retina. 2024;44(3):487-497. PMID: 38227884
- Merry GF, et al. PBM reduces drusen volume and improves visual acuity. Acta Ophthalmol. 2017;95(4):e270-e277. PMID: 28120450
- Ivandic BT, Ivandic T. Low-level laser therapy improves vision in AMD. Photomed Laser Surg. 2008;26(3):241-245. PMID: 18588438
- Yi C, Pan X, et al. Effects of melatonin in AMD. Ann N Y Acad Sci. 2005;1057:384-392. PMID: 16399908
- Saini JS, et al. Nicotinamide Ameliorates Disease in AMD iPSC Model. Cell Stem Cell. 2017;20(5):635-647. PMID: 28132833
- Cimaglia G, et al. NAD+ supplementation for glaucoma and AMD. Nutrients. 2020;12(9):2871. PMID: 32962222
- Burton B, Parodi MB, Jürgens I, et al. LIGHTSITE II Randomized Multicenter Trial. Ophthalmol Ther. 2023;12(2):953-968. PMID: 36690910
Chapter 6: The Critical Role of Carbon Dioxide
- Harino S, Grunwald JE, et al. Rebreathing into a bag increases macular blood flow. Br J Ophthalmol. 1995;79(5):483-486. PMID: 7612564
- Rivers RJ, Meininger CJ. Therapeutic potential of carbon dioxide therapy. 2023. PMC10048965
- Stefansson E, et al. Dorzolamide increases retinal oxygen tension. Invest Ophthalmol Vis Sci. 2004. PMID: 15742212
- Scozzafava A, Supuran CT, Carta F. Carbonic Anhydrases and Metabolism. Metabolites. 2020;10(10):412. PMID: 33076527
- Subramanian VS, et al. Vitamin B1 (thiamine) uptake by human RPE cells. J Physiol. 2006;571(Pt 2):363-373. PMID: 16410284
- Gratton SM, Lam BL. Visual loss and optic nerve swelling in thiamine deficiency. Clin Ophthalmol. 2014;8:1021-1024. PMID: 24920884
- Vitamin B1 intake inversely associated with late AMD prevalence. 2023. PMID: 37926095
- Hammes HP, et al. Benfotiamine blocks hyperglycemic damage and prevents diabetic retinopathy. Nat Med. 2003;9(3):294-299. PMID: 12592403
- Yadav UC, et al. Prevention of Endotoxin-Induced Uveitis by Benfotiamine. Invest Ophthalmol Vis Sci. 2010;51(4):2158-2165. PMID: 19933189
Chapter 7: Optimizing Oxygen Delivery
- De Lorenzo A, et al. Seasonal variations of rheological parameters. Arterioscler Thromb Vasc Biol. 1997;17(11):2692-2697.
- Keatinge WR, et al. Blood viscosity and arterial pressure during surface cooling. BMJ. 1984;289(6456):1405-1408. PMID: 6437575
- Ernst E, et al. Sauna effects on hemorheology. Arch Phys Med Rehabil. 1986;67(8):526-529. PMID: 3741077
- Scoon GS, et al. Post-exercise sauna and endurance performance. J Sci Med Sport. 2007;10(4):259-262. PMID: 16877041
- EPO treatment in hemodialysis patients: 43% lower AMD risk. 2022. PMID: 36077032
- Grimm C, Wenzel A. Erythropoietin: potential use in atrophic AMD. Mol Vis. 2009. PMID: 19128888
- Bachman E, et al. Testosterone induces erythrocytosis via EPO. J Gerontol A. 2014;69(6):725-735. PMID: 24158761
- Keszler A, et al. Red/NIR light rescues vascular dysfunction in diabetes. Free Radic Biol Med. 2017;113:157-164. PMID: 28927764
- Yokomizo S, et al. NIR-II photobiomodulation augments nitric oxide. FASEB J. 2022;36(8):e22490. PMID: 35838722
Chapter 8: Addressing Systemic Factors
- Crabb JW, et al. Drusen proteome analysis. Proc Natl Acad Sci U S A. 2002;99(23):14682-14687. PMID: 12391305
- AREDS Research Group. Arch Ophthalmol. 2001;119(10):1417-1436. PMID: 11594942
- AREDS2 Research Group. JAMA. 2013;309(19):2005-2015. PMID: 23644932
- Ugarte M, Osborne NN. Zinc in the retina. Prog Neurobiol. 2001;64(3):219-249. PMID: 11240307
- Bernstein PS, et al. Macular pigment. Prog Retin Eye Res. 2016;50:34-66. PMID: 26541886
- Richer S, et al. Resveratrol in AMD. Nutrients. 2013;5(6):1989-2005. PMID: 23736827
- Schurgers LJ, et al. Vitamin K2 and vascular calcification. Trends Mol Med. 2013;19(4):217-226. PMID: 23375872
- Christen WG, et al. Vitamin D and AMD in VITAL trial. JAMA Ophthalmol. 2020;138(12):1280-1289. PMID: 33119047
- Hageman GS, et al. Complement factor H polymorphism and AMD. Proc Natl Acad Sci U S A. 2005;102(20):7227-7232. PMID: 15870199
- Glenn JV, Stitt AW. AGEs and AMD. Biochim Biophys Acta. 2009;1790(10):1109-1116. PMID: 19406212
Chapter 9: Mobilizing Repair
- Dow CT, Harley CB. Oral telomerase activator for early AMD. Clin Ophthalmol. 2016;10:243-249. PMID: 26869760
- Salvador L, Singaravelu G, et al. Natural telomerase activator lengthens telomeres. Rejuvenation Res. 2016;19(6):478-484. PMID: 26950204
- Fahy GM, Brooke RT, et al. Reversal of epigenetic aging in humans. Aging Cell. 2019;18(6):e13028. PMID: 31496122
- Thom SR, Bhopale VM, et al. Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol. 2006;290(4):H1378-H1386. PMID: 16299259
- Jensen GS, Hart AN, et al. Mobilization of CD34+ stem cells by AFA consumption. Cardiovasc Revasc Med. 2007;8(3):189-202. PMID: 17765649
- Agha NH, Baker FL, et al. Vigorous exercise mobilizes CD34+ stem cells. Brain Behav Immun. 2018;68:66-75. PMID: 29017969
- Cheng CW, Adams GB, et al. Prolonged fasting promotes stem cell regeneration. Cell Stem Cell. 2014;14(6):810-823. PMID: 24905167
- Shen Y, Wang J, et al. 830 nm PBM promotes stem cell engraftment. Sci Rep. 2020;10(1):19687. PMID: 33184331
Chapter 10: Lifestyle Interventions
- Cho E, et al. Dietary fat and AMD risk. Am J Clin Nutr. 2001;73(2):209-218. PMID: 11157315
- Simopoulos AP. Omega-6/omega-3 ratio in chronic diseases. Exp Biol Med. 2008;233(6):674-688. PMID: 18408140
- Chiu CJ, et al. Dietary glycemic index and early AMD. Am J Clin Nutr. 2006;83(4):880-886. PMID: 16600941
- Boyer DS, et al. LIGHTSITE III: PBM in dry AMD. Retina. 2024;44(3):487-497. PMID: 38227884
- McGuinness MB, et al. Physical Activity and AMD: Meta-analysis. Am J Ophthalmol. 2017;180:29-38. PMID: 28549846
- Knudtson MD, et al. Physical activity and AMD incidence: Beaver Dam Eye Study. Br J Ophthalmol. 2006;90(12):1461-1463. PMID: 16873390
- Li S, et al. Sleep duration and AMD: Mendelian randomization. Front Aging Neurosci. 2023;15:1247413. PMID: 37693650
- Cohen-Tayar Y, et al. Melatonin and AMD Risk. JAMA Ophthalmol. 2024;142(7):620-627. PMID: 38842832
- Sabel BA, et al. Mental stress as cause of vision loss. EPMA J. 2018;9(2):133-160. PMID: 29896314
Chapter 11: Anti-Aging Interventions
- Blasiak J. Cellular senescence in AMD: autophagy and DNA damage. Oxid Med Cell Longev. 2017;2017:5293258. PMID: 28751931
- Ratnayaka JA, et al. Amyloid beta in retinal degeneration. Eye (Lond). 2015;29(8):1013-1026. PMID: 26088679
- Kirkland JL, Tchkonia T. Senolytic drugs: discovery to translation. J Intern Med. 2020;288(5):518-536. PMID: 32686219
- Dasatinib and Quercetin alleviates lipofuscin-dependent retinal degeneration. Redox Biol. 2025;79:103486.
- Yousefzadeh MJ, et al. Fisetin is a senotherapeutic that extends lifespan. EBioMedicine. 2018;36:18-28. PMID: 30279143
- Telegina DV, et al. SkQ1 Visomitin eye drops suppress p38 MAPK signaling. Biochemistry (Moscow). 2024;89(2):222-234. PMID: 38622090
- Markovets AM, et al. SkQ1 therapeutic action on retinopathy in OXYS rats. PLoS One. 2011;6(7):e21682. PMID: 21750722
- Anisimov VN, et al. Epitalon effects on aging biomarkers and lifespan. Biogerontology. 2003;4(4):193-202. PMID: 14501183
- Allan JR, et al. GLP-1 RA impact on AMD. Ophthalmology. 2025. PMID: 39863057
- Shor R, Mihalache A, et al. GLP-1 RA and neovascular AMD risk. JAMA Ophthalmol. 2025.