Dietary supplements in retinal diseases, glaucoma, and other ocular conditions


Ocular diseases
Retinal diseases
Med Diet


Environmental pollution, inadequate eating habits and unhealthy lifestyles have led to a tremendous increase in ocular diseases worldwide. Given the costly treatments that are currently available for the most common and threatening eye diseases (such as cataract, dry eye disorder, or diabetic retinopathy), curing these diseases or preventing refractive errors by taking nutraceuticals and natural compounds that are present in our daily diet is a very valuable intervention. The eyes are the most important part of our visual system and require micronutrients such as vitamins, carotenoids, trace metals, and omega-3 fatty acids in order to function properly and to protect themselves against light-induced and age-mediated degenerative disorders. The Mediterranean Diet (MedDiet) has been in the limelight since the 1980s because of the several health benefits it provides, including eye health. MedDiet is characterized by the consumption of small amounts of red meat, while emphasizing the intake of fish, eggs, nuts, legumes, citrus fruits, green vegetables, olives and their derivatives, especially olive oil, and dairy products in a proportionate manner, in order to achieve the maximum health benefits. The antioxidant, anti-inflammatory, and neuroprotective properties of these foods – both when used as an ingredient in the dietary regime or as a source of nutritional supplements – have shown promising results in the management of chronic degenerative ocular diseases, both in animal models and in human subjects. In this chapter, we will focus on the importance of MedDiet and natural compounds for the visual system and its role in slowing down age-related ocular degeneration.


[1] Valero-Vello M, Peris-Martínez C, García-Medina JJ, Sanz-González SM, Ramírez AI, Fernández-Albarral JA, Galarreta-Mira D, Zanón-Moreno V, Casaroli-Marano RP, Pinazo-Duran, MD. Searching for the antioxidant, anti-inflammatory, and neuroprotective potential of natural food and nutritional supplements for ocular health in the mediterranean population. Foods 2021;10:1231.
[2] Burton MJ, Ramke J, Marques AP, Bourne RRA, Congdon N, Jones I, Ah Tong BAM, Arunga S, Bachani D, Bascaran C, Bastawrous A, Blanchet K, Braithwaite T, Buchan JC, Cairns J, Cama A, Chagunda M, Chuluunkhuu C, Cooper A, Crofts-Lawrence J, Dean WH, Denniston AK, Ehrlich JR, Emerson PM, Evans JR, Frick KD, Friedman DS, Furtado JM, Gichangi MM, Gichuhi S, Gilbert SS, Gurung R, Habtamu E, Holland P, Jonas JB, Keane PA, Keay L, Khanna RC, Khaw PT, Kuper H, Kyari F, Lansingh VC, Mactaggart I, Mafwiri MM, Mathenge W, McCormick I, Morjaria P, Mowatt L, Muirhead D, Murthy GVS, Mwangi N, Patel DB, Peto T, Qureshi BM, Salomão SR, Sarah V, Shilio BR, Solomon AW, Swenor BK, Taylor HR, Wang N, Webson A, West SK, Wong TY, Wormald R, Yasmin S, Yusufu M, Silva JC, Resnikoff S, Ravilla T, Gilbert CE, Foster A, Faal HB. The Lancet Global Health Commission on Global Eye Health: vision beyond 2020. Lancet Glob Health 2021:9:e489-e551.
[3] Falsini B, Placidi G, De Siena E, Savastano MC, Minnella AM, Maceroni M, Midena G, Ziccardi L, Parisi V, Bertelli M, Maltese PE, Chiurazzi P, Rizzo S. USH2A-Related Retinitis Pigmentosa: staging of disease severity and morpho-functional studies. Diagnostics (Basel) 2021;11:213.
[4] Marino V, Dal Cortivo G, Maltese PE, Placidi G, De Siena E, Falsini B, Bertelli M, Dell’Orco D. Impaired Ca2+ sensitivity of a novel GCAP1 variant causes cone dystrophy and leads to abnormal synaptic transmission between photoreceptors and bipolar cells. Int J Mol Sci 2021;22:4030.
[5] Falsini B, Placidi G, De Siena E, Chiurazzi P, Minnella AM, Savastano MC, Ziccardi L, Parisi V, Iarossi G, Percio M, Piteková B, Marceddu G, Maltese PE, Bertelli M. Genetic characteristics of 234 Italian patients with macular and cone/ cone-rod dystrophy. Sci Rep 2022;12:3774.
[6] Colombo L, Maltese PE, Castori M, El Shamieh S, Zeitz C, Audo I, Zulian A, Marinelli C, Benedetti S, Costantini A, Bressan S, Percio M, Ferri P, Abeshi A, Bertelli M, Rossetti L. Molecular epidemiology in 591 italian probands with nonsyndromic retinitis pigmentosa and usher syndrome. Invest Ophthalmol Vis Sci 2021;62:13.
[7] Zhang J, Tuo J, Wang Z, Zhu A, Machalińska A, Long Q. Pathogenesis of Common Ocular Diseases. J Ophthalmol 2015:734527.
[8] Lanzetta P, Sarao V, Scanlon PH, Barratt J, Porta M, Bandello F, Loewenstein A, Vision Academy. Fundamental principles of an effective diabetic retinopathy screening program. Acta Diabetol 2020;57:785-98.
[9] Pondorfer SG, Terheyden JH, Heinemann M, Wintergerst MWM, Holz FG, Finger RP. association of vision-related quality of life with visual function in age-related macular degeneration. Sci Rep 2019;9:15326.
[10] Glewwe Paul, West KL, Lee J. The Impact of Providing Vision screening and free eyeglasses on academic outcomes: evidence from a randomized trial in title i elementary schools in Florida. J Policy Anal Manage 2018;37:265-300.
[11] Hannum E, Zhang Y. poverty and proximate barriers to learning: vision deficiencies, vision correction and educational outcomes in rural northwest China. World Dev 2012;40:1921-31.
[12] Pinazo-Durán MD, Muñoz-Negrete FJ, Sanz-González SM, Benítez-Del-Castillo J, Giménez-Gómez R, Valero-Velló M, Zanón-Moreno V, García-Medina JJ. The role of neuroinflammation in the pathogenesis of glaucoma neurodegeneration. Prog Brain Res 2020;256:99-124.
[13] Khanna S, Komati R, Eichenbaum DA, Hariprasad I, Ciulla TA, Hariprasad SM. Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review. BMJ Open Ophthalmol 2019;4:e000398.
[14] Gahn G, Khanani A. New therapies of neovascular AMD beyond Anti-VEGF injections. Vision 2018;2:15.
[15] Yerramothu P. New therapies of neovascular AMD–beyond anti-VEGFs. Vision 2018;2:31.
[16] French S. visual impairment and work: experiences of visually impaired people. 1st Edition. Routledge 2017.
[17] Brunes AB, Hansen M, Heir T. Loneliness among adults with visual impairment: prevalence, associated factors, and relationship to life satisfaction. Health Qual Life Outcomes 2019;17:24.
[18] Bernabei V, Morini V, Moretti F, Marchiori A, Ferrari B, Dalmonte E, De Ronchi D, Atti AR. Vision and hearing impairments are associated with depressive–anxiety syndrome in Italian elderly. Aging Ment Health 2011;15:467-74.
[19] Kuźma E, Littlejohns TJ, Khawaja AP, Llewellyn DJ, Ukoumunne OC, Thiem U. Visual impairment, eye diseases, and dementia risk: a systematic review and meta-analysis. J Alzheimers Dis 2021;83:1073-87.
[20] Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 1993;111:761-72.
[21] West K. Vitamin A deficiency disorders in children and women. Food Nutr Bull 2003;24:S78-S90.
[22] Semba RD. Nutritional amblyopia and B complex vitamin deficiencies. In: Handbook of Nutrition and Ophthalmology 2007:281-354.
[23] Vishwanathan R, Johnson EJ. Lutein and zeaxanthin and eye disease. In: Tanumihardjo S, eds. Carotenoids and Human Health. Nutrition and Health. Totowa, NJ: Humana Press 2013.
[24] Georgousopoulou EN, Mellor DD, Naumovski N, Polychronopoulos E, Tyrovolas S, Piscopo S, Valacchi G, Anastasiou F, Zeimbekis A, Bountziouka V, Gotsis E, Metallinos G, Tyrovola D, Foscolou A, Tur JA, Matalas AL, Lionis C, Sidossis L, Panagiotakos D; MEDIS study group. Mediterranean lifestyle and cardiovascular disease prevention. Cardiovasc Diagn Ther 2017;7:S39-S47.
[25] Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to Mediterranean diet and health status: meta-analysis. BMJ 2008;337:a1344-a1344.
[26] Feldman E. Mediterranean diet and frailty risk. Integrative Medicine Alert 2018;21. Available at: https://www.reliasmedia. com/articles/142449-mediterranean-diet-and-frailty-risk. Accessed on: 02/08/2022
[27] Keenan TD, Agrón E, Mares J, Clemons TE, van Asten F, Swaroop A, Chew EY, age-related eye disease studies (AREDS) 1 and 2 Research Groups. Adherence to the Mediterranean Diet and Progression to Late Age-Related Macular Degeneration in the Age-Related Eye Disease Studies 1 and 2. Ophthalmology 2020;127:1515-28. ophtha.2020.04.030
[28] Merle B, Colijn JM, Cougnard-Grégoire A, de Koning-Backus A, Delyfer MN, Kiefte-de Jong JC, Meester-Smoor M, Féart C, Verzijden T, Samieri C, Franco OH, Korobelnik JF, Klaver C, Delcourt C; EYE-RISK Consortium. Mediterranean Diet and incidence of advanced age-related macular degeneration: The EYE-RISK Consortium. Ophthalmology 2019;126:381-90.
[29] Moïse MM, Benjamin LM, Doris TM, Dalida KN, Augustin NO. Role of Mediterranean diet, tropical vegetables rich in antioxidants, and sunlight exposure in blindness, cataract and glaucoma among African type 2 diabetics. Int J Ophthalmol 2012;5:231-7.
[30] Dighe S, Zhao J, Steffen L, Mares JA, Meuer SM, Klein B, Klein R, Millen AE. Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study. Br J Ophthalmol 2020;104:1070-6.
[31] Napolitano P, Filippelli M, Davinelli S, Bartollino S, dell’Omo R, Costagliola C. Influence of gut microbiota on eye diseases: an overview. Ann Med 2021;53:750-61.
[32] Rinninella E, Mele M, Merendino N, Cintoni M, Anselmi G, Caporossi A, Gasbarrini A, Minnella A. The role of diet, micronutrients and the gut microbiota in age-related macular degeneration: new perspectives from the gut–retina axis. Nutrients 2018;10:1677.
[33] Khan A, Ding Z, Ishaq M, Bacha AS, Khan I, Hanif A, Li W, Guo X. understanding the effects of gut microbiota dysbiosis on nonalcoholic fatty liver disease and the possible probiotics role: recent updates. Int J Biol Sci 2021;17:818-33.
[34] Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 2021;19:55-71.
[35] Meng X, Li Y, Li S, Zhou Y, Gan RY, Xu DP, Li HB. Dietary sources and bioactivities of melatonin. Nutrients 2017;9:367.
[36] Garcia-Mantrana I, Selma-Royo M, Alcantara C, Collado MC. Shifts on gut microbiota associated to mediterranean diet adherence and specific dietary intakes on general adult population. Front Microbiol 2018;9:890.
[37] Mitsou EK, Kakali A, Antonopoulou S, Mountzouris KC, Yannakoulia M, Panagiotakos DB, Kyriacou A. Adherence to the Mediterranean diet is associated with the gut microbiota pattern and gastrointestinal characteristics in an adult population. Br J Nutr 2017;117:1645-55.
[38] De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, Serrazanetti DI, Di Cagno R, Ferrocino I, Lazzi C, Turroni S, Cocolin L, Brigidi P, Neviani E, Gobbetti M, O’Toole PW, Ercolini D. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut 2016;65:1812-21.
[39] Cavuoto KM, Banerjee S, Galor A. Relationship between the microbiome and ocular health. Ocul Surf 2019;17:384-92.
[40] Gillette MU, McArthur AJ. Circadian actions of melatonin at the suprachiasmatic nucleus. Behav Brain Res 1996;73:135-9.
[41] Mul Fedele ML, Galiana MD, Golombek DA, Muñoz EM, Plano SA. Alterations in metabolism and diurnal rhythms following bilateral surgical removal of the superior cervical ganglia in rats. Front Endocrinol (Lausanne) 2018;8:370.
[42] Mayo JC, Sainz RM. Melatonin from an antioxidant to a classic hormone or a tissue factor: experimental and clinical aspects 2019. Int J Mol Sci 2020;21:3645.
[43] Moradkhani F, Moloudizargari M, Fallah M, Asghari N, Khoei HH, Asghari MH. Immuno-regulatory role of melatonin in cancer. J Cell Physiol 2019;235:745-57.
[44] Legros C, Dupré C, Brasseur C, Bonnaud A, Bruno O, Valour D, Shabajee P, Giganti A, Nosjean O, Kenakin TP, Boutin JA. Characterization of the various functional pathways elicited by synthetic agonists or antagonists at the melatonin MT1 and MT2 receptors. Pharmacol Res Perspect 2019;8:e00539.
[45] Nosjean O, Nicolas JP, Klupsch F, Delagrange P, Canet E, Boutin JA. Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2. Biochem Pharmacol 2001;61:1369-79.[01]00615-3
[46] Andrews CD, Foster RG, Alexander I, Vasudevan S, Downes SM, Heneghan C, Plüddemann A. Sleep-wake disturbance related to ocular disease: a systematic review of phase-shifting pharmaceutical therapies. Transl Vis Sci Technol 2019;8:49.
[47] Carracedo G, Carpena C, Concepción P, Díaz V, García-García M, Jemni N, Lledó VE, Martín M, Pastrana C, Pelissier R, Veselinova A, Wang X, Pintor J. Presence of melatonin in human tears. J Optom 2017;10:3-4.
[48] Rada JA, Wiechmann AF. Melatonin receptors in chick ocular tissues: implications for a role of melatonin in ocular growth regulation. Invest Ophthalmol Vis Sci 2006;47:25-33.
[49] Alkozi HA, Navarro G, Franco R, Pintor J. Melatonin and the control of intraocular pressure. Prog Retin Eye Res 2020;75:100798.
[50] Aranda ML, Fleitas MFG, Dieguez H, Iaquinandi A, Sande PH, Dorfman D, Rosenstein RE. Melatonin as a Therapeutic Resource for Inflammatory Visual Diseases. Curr Neuropharmacol 2017;15:951-62. 159X15666170113122120
[51] Martínez-Águila A, Martín-Gil A, Carpena-Torres C,Pastrana C, Carracedo G. Influence of circadian rhythm in the eye: significance of melatonin in glaucoma. Biomolecules 2021;11:340.
[52] Gubin D, Neroev V, Malishevskaya T, Cornelissen G, Astakhov SY, Kolomeichuk S, Yuzhakova N, Kabitskaya Y, Weinert D. Melatonin mitigates disrupted circadian rhythms, lowers intraocular pressure, and improves retinal ganglion cells function in glaucoma. J Pineal Res 2021;70:e12730.
[53] Diéguez HH, González Fleitas MF, Aranda ML, Calanni JS, Keller Sarmiento MI, Chianelli MS, Alaimo A, Sande PH, Romeo HE, Rosenstein RE, Dorfman D. Melatonin protects the retina from experimental nonexudative age-related macular degeneration in mice. J Pineal Res 2020;68:e12643.
[54] Ferreira de Melo IM, Martins Ferreira CG, Lima da Silva Souza EH, Almeida LL, Bezerra de Sá F, Cavalcanti Lapa Neto CJ, Paz de Castro MV, Teixeira VW, Coelho Teixeira ÁA. Melatonin regulates the expression of inflammatory cytokines, VEGF and apoptosis in diabetic retinopathy in rats. Chem Biol Interact 2020;327:109183.
[55] Klettner A, Kampers M, Töbelmann D, Roider J, Dittmar M. The Influence of Melatonin and Light on VEGF Secretion in Primary RPE Cells. Biomolecules 2021;11:114.
[56] Castelli V, Paladini A, d’Angelo M, Allegretti M, Mantelli F, Brandolini L, Cocchiaro P, Cimini A, Varrassi G. Taurine and oxidative stress in retinal health and disease. CNS Neurosci Ther 2021;27:403-12.
[57] El-Sherbeny A, Naggar H, Miyauchi S, Ola MS, Maddox DM, Martin PM, Ganapathy V, Smith SB. Osmoregulation of taurine transporter function and expression in retinal pigment epithelial, ganglion, and müller cells. Invest Ophthalmol Vis Sci 2004;45:694-701.
[58] Tomi M, Tajima A, Tachikawa M, Hosoya K. Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells. Biochim Biophys Acta 2008;1778:2138-42.
[59] García-Ayuso D, Di Pierdomenico J, Hadj-Said W, Marie M, Agudo-Barriuso M, Vidal-Sanz M, Picaud, Serge; Villegas-Pérez MP. Taurine depletion causes ipRGC loss and increases light-induced photoreceptor degeneration. Invest Ophthalmol Vis Sci 2018;59:1396.
[60] Cammalleri M, Dal Monte M, Amato R, Bagnoli P, Rusciano D. A dietary combination of forskolin with homotaurine, spearmint and b vitamins protects injured retinal ganglion cells in a rodent model of hypertensive glaucoma. Nutrients 2020;12:1189.
[61] Froger N, Moutsimilli L, Cadetti L, Jammoul F, Wang QP, Fan Y, Gaucher D, Rosolen SG, Neveux N, Cynober L, Sahel JA, Picaud S. Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations. Prog Retin Eye Res 2014;41:44-63.
[62] Bastaki SM, Adeghate E, Amir N, Ojha S, Oz M. Menthol inhibits oxidative stress and inflammation in acetic acid-induced colitis in rat colonic mucosa. Am J Transl Res 2018;10:4210-22.
[63] Kiani AK, Falsini B, Ziccardi L, Gusson E, Mangialavori D, Allegrini F, Colao E, Bertelli M. Flavonoid supplements increase neurotrophin activity to modulate inflammation in retinal genetic diseases. Acta Biomed 2020;91:e2020014.
[64] Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the women’s antioxidant and folic acid cardiovascular study. Arch Intern Med 2009;169:335-41.
[65] Wang XB, Qiao C, Wei L, Han YD, Cui NH, Huang ZL, Li ZH, Zheng F, Yan M. Associations of polymorphisms in mthfr gene with the risk of age-related cataract in chinese han population: a genotype-phenotype analysis. PLoS One 2015;10:e0145581.
[66] Christen WG, Glynn RJ, Manson JE, MacFadyen J, Bubes V, Schvartz M, Buring JE, Sesso HD, Gaziano JM. Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 2014;121:525-34.
[67] Glaser TS, Doss LE, Shih G, Nigam D, Sperduto RD, Ferris FL 3rd, Agrón E, Clemons TE, Chew EY; Age-Related Eye Disease Study Research Group. The association of dietary lutein plus zeaxanthin and B vitamins with cataracts in the age-related eye disease study: AREDS Report No. 37. Ophthalmology 2015;122:1471-9.
[68] Tan AG, Mitchell P, Rochtchina E, Flood VM, Cumming RG, Wang JJ. Serum homocysteine, vitamin B12, and folate, and the prevalence and incidence of posterior subcapsular cataract. Invest Ophthalmol Vis Sci 2014;56:216-20.
[69] Molina-Leyva I, Molina-Leyva A, Bueno-Cavanillas A. Efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids in dry eye syndrome: a systematic review of randomized clinical trials. Acta Ophthalmol 2017;95:e677-e685.
[70] Zhang AC, Singh S, Craig JP, Downie LE. Omega-3 Fatty Acids and Eye Health: Opinions and Self-Reported Practice Behaviors of Optometrists in Australia and New Zealand. Nutrients 2020;12:1179.
[71] Meyer BJ. Australians are not meeting the recommended intakes for omega-3 long chain polyunsaturated fatty acids: results of an analysis from the 2011-2012 national nutrition and physical activity survey. Nutrients 2016;8:111.
[72] Rand AL, Asbell PA. Nutritional supplements for dry eye syndrome. Curr Opin Ophthalmol 2011;22:279-82.
[73] Walter SD, Gronert K, McClellan AL, Levitt RC, Sarantopoulos KD, Galor A. ω-3 tear film lipids correlate with clinical measures of dry eye. Invest Ophthalmol Vis Sci 2016;57:2472-8.
[74] Miljanović B, Trivedi KA, Dana MR, Gilbard JP, Buring JE, Schaumberg DA. Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. Am J Clin Nutr 2005;82:887-93.
[75] van Leeuwen EM, Emri E, Merle BMJ, Colijn JM, Kersten E, Cougnard-Gregoire A, Dammeier S, Meester-Smoor M, Pool FM, de Jong EK, Delcourt C, Rodrigez-Bocanegra E, Biarnés M, Luthert PJ, Ueffing M, Klaver CCW, Nogoceke E, den Hollander AI, Lengyel I. A new perspective on lipid research in age-related macular degeneration. Prog Retin Eye Res 2018;67:56-86.
[76] Simón MV, Agnolazza DL, German OL, Garelli A, Politi LE, Agbaga MP, Anderson RE, Rotstein NP. Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress. J Neurochem 2016;136:931-46.
[77] Tan JS, Wang JJ, Flood V, Mitchell P. Dietary fatty acids and the 10-year incidence of age-related macular degeneration: the Blue Mountains Eye Study. Arch Ophthalmol 2009;127:656-65.
[78] Wu J, Cho E, Giovannucci EL, Rosner BA, Sastry SM, Willett WC, Schaumberg DA. Dietary intakes of eicosapentaenoic acid and docosahexaenoic acid and risk of age-related macular degeneration. Ophthalmology 2017;124:634-43.
[79] Lawrenson JG, Evans JR. Omega 3 fatty acids for preventing or slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev 2015;2015:CD010015.
[80] Downie LE, Vingrys AJ. Oral omega-3 supplementation lowers intraocular pressure in normotensive adults. Transl Vis Sci Technol 2018;7:1.
[81] Keppel Hesselink JM, Costagliola C, Fakhry J, Kopsky DJ. Palmitoylethanolamide, a natural retinoprotectant: its putative relevance for the treatment of glaucoma and diabetic retinopathy. J Ophthalmol 2015;2015:430596.
[82] Ye S, Chen Q, Jiang N, Liang X, Li J, Zong R, Huang C, Qiu Y, Ma JX, Liu Z. PPARα-Dependent effects of palmitoylethanolamide against retinal neovascularization and fibrosis. Invest Ophthalmol Vis Sci 2020;61:15.
[83] Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, de Jong PT, Klaver CC, Klein BE, Klein R. The International ARM Epidemiological Study Group. An international classification and grading system for age-related maculopathy and age-related macular degeneration. Surv Ophthalmol 1995;39:367-74.
[84] Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000;45:115-34.
[85] Buschini E, Piras A, Nuzzi R, Vercelli A. Age related macular degeneration and drusen: neuroinflammation in the retina. Prog Neurobiol 2011;95:14-25. pneurobio.2011.05.011
[86] Hollyfield JG. Age-related macular degeneration: the molecular link between oxidative damage, tissue-specific inflammation and outer retinal disease: the Proctor lecture. Invest Ophthalmol Vis Sci 2010;51:1275-81.
[87] Jarrett SG, Boulton ME. Consequences of oxidative stress in age-related macular degeneration. Mol Aspects Med 2012;33:399-417.
[88] Marangoni D, Falsini B, Piccardi M, Ambrosio L, Minnella AM, Savastano MC, Bisti S, Maccarone R, Fadda A, Mello E, Concolino P, Capoluongo E. Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report. J Transl Med 2013;11:228.
[89] Swaroop A, Chew EY, Rickman CB, Abecasis GR. Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. Annu Rev Genomics Hum Genet 200;10:19-43.
[90] Maccarone R, Di Marco S, Bisti S. Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Invest Ophthal Visual Sci 2008;49:1254-61.
[91] Falsini B, Piccardi M, Minnella A, Savastano C, Capoluongo E, Fadda A, Balestrazzi E, Maccarone R, Bisti S. Influence of saffron supplementation on retinal flicker sensitivity in early age related macular degeneration. Invest Ophthalmol Vis Sci 2010;51:6118-24.
[92] Piccardi M, Marangoni D, Minnella AM, Savastano MC, Valentini P, Ambrosio L, Capoluongo E, Maccarone R, Bisti S, Falsini B. A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function. Evid Based Complement Alternat Med 2012;429124.
[93] Giaccio M. Crocetin from saffron: an active component of an ancient spice. Crit Rev Food Sci Nutr 2004;44:155-72.
[94] Ochiai T, Shimeno H, Mishima K, Iwasaki K, Fujiwara M, Tanaka H, Shoyama Y, Toda A, Eyanagi R, Soeda S. Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo. Biochem Biophys Acta 2007;1770:578-84.
[95] Di Marco F, Romeo S, Nandasena C, Purushothuman S, Adams C, Bisti S, Stone J. The time course of action of two neuroprotectants, dietary saffron and photobiomodulation, assessed in the rat retina. Am J Neurodegener Dis 2013;2:208-20.
[96] Kanakis CD, Tarantilis PA, Tajimir-Riahi HA, Polissiou MG. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J Agric Food Chem 2007;55:970-7.
[97] Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, Jung WS, Cho KH, Park JH, Kang I, Hong JW, Lee EH. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol 2010;648:110-6.
[98] Natoli R, Zhu Y, Valter K, Bisti S, Eells J, Stone J. Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina. Mol Vis 2010;16:1801-22.