Introduction: macular degeneration supplement Saffron 2020 helps you maintain eyesight; learn how?

Good nutrition is very important for general health and more specifically for eye health. Good nutrition helps our body grow, repair the wear and tear caused by the aging process, and to function properly.

In various studies and clinical trials, anretioxidant vitamins and phytochemicals found in certain foods have been linked with better eye health. They help to maintain healthy cells and tissues in the eye.

It is known that the retina needs key anti-oxidants – lutein and zeaxanthin, and also vitamins A, B2, C and E, and zinc – to protect itself from daily oxidative damage. Anti-oxidants are substances that may protect the cells against the effects of free radicals, the molecules produced when the body breaks down food or fights infection, or when exposed to environmental stressors like air pollution, tobacco smoke and radiation. Once they are produced they can damage other cells. They are believed to play a part both in the natural aging process and in age-related vision loss.

Two large clinical trials, called the ‘Age-Related Eye Disease Study’ (AREDS) showed that antioxidant vitamins C, E, and the minerals zinc as zinc oxide, and copper as cupric oxide, can help to slow down the progression of age-related macular degeneration (AMD).

Following the two AREDS clinical trials there have been over 150 smaller scale studies looking at how vitamins and minerals, both from food and in a vitamin supplement can help eye health in general, and in particular AMD and cataracts. A number of recent studies have looked specifically at saffron, resveratrol, lutein and zeaxanthin, which have been associated with healthy eyes and protection against damage to retina. Studies have shown how these ingredients can modulate the function of retinal genes, stimulate repair mechanism, protect against oxidative and inflammatory damage and help preserve eyesight.

Research has shown that many people do not get enough vitamins, minerals and important eye nutrients from their diet, and therefore some people might consider taking a supplement for their general health and for eye health.

Use of nutritional supplements has given a hope for development of new natural remedies for ameliorating age-associated loss of eyesight and against eye diseases such as AMD and cataracts, and for decelerating disease progression as a function of adult age.

Age-related macular degeneration (AMD)

Age-related macular degeneration (AMD) is a leading cause of adult vision loss in developed countries and accounts for more than 50% of blindness in the United States, and the number of individuals affected is expected to double in 2020. (Huang et al. 2008; National Eye Institute. Vision problems in the US 2006).

It is estimated that there are over 20 million cases of AMD in the US and Europe, and up to 17 million elderly have at least early signs of AMD called Age Related Maculopathy (ARM) [www.nei.nih.gov/eyedata]).

The worldwide incidence of the disease increases from one in ten people over the age of 60 to more than 1 in 4 people over the age of 75. According to AMD Alliance, macular degeneration is more common than Parkinson’s disease, Alzheimer’s disease, breast cancer and prostate cancer combined. The resulting visual impairment from AMD disease affects patient’s quality of life, and the individual’s emotional and social health, as well as independence is adversely affected.

AMD causes high economic burden to the society and health care system because inflicted patients with impaired vision have an increased risk of fall, fracture, and depression and need daily support services or nursing home care.

AMD is becoming a major public health concern because the population is ageing and as a direct result an increase in incidence is awaited.

Although vision loss is becoming a major public health problem, current therapy options for AMD, specially for the dry form of AMD are limited, and therefore, preventive interventions specially novel nutritional supplements are needed for reducing this increasing burden on society. Nutritional supplements have particular role in managing AMD and cataracts (Huang et al. 2008).

Pathology of age-related macular degeneration or AMD:

Vision loss in patients with AMD is attributable to photoreceptor death in central retina. Growing scientific evidence suggests a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The early stage of pathogenesis is associated with degeneration of retinal pigment epithelial (RPE) cells, which are responsible for degradation of photoreceptor outer segments that have been shed. RPE death leads to photoreceptor death (Sheu et al. 2010). The retina is particularly susceptible to oxidative damage because of its high consumption of oxygen, the transparency of the cornea, aqueous humour and lens that allow continuous exposure of retina to light creating an intrinsic vulnerability of the retina to damage via oxidative stress.

Risk factors affecting development of AMD include age greater than 50, Caucasian race, nutrition, smoking, atherosclerotic vascular disease, genetics, and sunlight exposure (Sheu et al. 2010; Thornton et al. 2005)

Role of nutrition in preserving eye health and protecting against AMD:

Several epidemiological studies have suggested a link between low consumption of carotenoids and antioxidant vitamins and minerals with increased risk of development and progression of AMD and cataracts (Kubota et al. 2009; Chucair et al. 2007; Bartlett & Eperjesi, 2003(B); Evans, 2006).

The use of nutritional supplements for improving health, protecting eysight and delaying age-related chronic diseases has become a common practice and standard of care (Maraini et al. 2009; Joseph et al.2009; and Jones 2007).

Antioxidant micronutrients such as, zinc and copper facilitate activity of antioxidant enzymes such as catalase and peroxidase in the body. Zinc also acts as a prosthetic group for the antioxidant enzyme superoxide dismutase, which will be unable to function in the absence of the prosthetic group. Similarly, other nutrients such as vitamin E, vitamin C and lutein and zeaxanthin have also shown to possess biological antioxidative properties protecting retinal cells against photoxidative damage (Bartlett & Eperjesi, 2004).

 

Role of special nutrients and plant extracts in eye health and macular degeneration:

Saffron for eye health in age-related macular degeneration (AMD) and cataracts:

Saffron (Crocus sativus) is a spice containing the antioxidant carotenoids crocin and crocetin. Saffron has been known for its antioxidant, anti-inflammator, and cell protective effects. Daily doses of up to 1.5 g are thought to be safe (Schmidt et al. 2007). Crocin, which is the main carotenoid in saffron has a stronger antioxidant activity than ?-tocopherol and can prevent the formation of peroxidized lipids and partly restore superoxide dismutase (SOD) activity (Ochiai et al. 2004).

A recent review on biological properties of saffron (Bathaie, & Mousavi, 2010) has indicated a wide range of useful biological properties in neuronal, cardiovascular, atherosclerosis, respiratory system, and blood pressure, and ocular benefits.

The most important result for eye health benefits of saffron came from a recent double blind, placebo-controlled, cross-over clinical study. Results indicated that taking oral supplementation of saffron at 20 mg/day for three months induced a short-term and significant improvement of retinal function in early AMD. In this study cone-mediated ERG in response to high-frequency flicker (focal ERG, FERG) was employed as the main outcome variable. The effects, however, disappeared when patients stopped taking the saffron pills. No adverse side effects were reported in this study.  According to Professor Silvia Bisti from the University of Sydney, who carried out the research, ‘Patients’ vision improved after taking the saffron pill’ (Falsini et al. 2010).

In a 15-month follow up clinical study, the same researchers observed that patients continued to get the benefits of the supplement for as long as they took the saffron capsules. This study confirmed initial findings that saffron may hold the key for tackling vision loss in AMD.

According to this recent study taking long term saffron supplement led to”improvement in contrast and colour perception, reading ability, and vision at low luminances, all ultimately leading to a substantial improvement in the patients’ quality of life.”

This new study showed that taking saffron supplementation for long term presents a safe natural solution to help prevent eyesight loss in old age, and as reported “no adverse systemic side effects were recorded” (Piccardi et al. 2012).

Age-related macular degeneration (ARMD)

Degeneration of the macula (the central part of the retina where the rods and cones are most dense) that leads to loss of central vision in people over 60.
….. Click the link for more information.The first report on eye health benefits of saffron and its main active compound, crocin, came from Xuan et al. (1999) that suggested crocin analogs can be used to treat ischemic retinopathy and/or age-related macular degeneration. The suggestion was based on the observation that intraperitoneal injection of crocin analogs (10 mg/Kg) significantly increased the blood flow in the retina and choroid.

The carotenoid crocin has protective effect against blue light- and white light-induced rod and cone death in bovine and primate retinal cell cultures. In the presence of 160mM crocin more than 90% of photoreceptors survived the effect of light exposure (Laabich et al. 2006). Light exposure leads to photoreceptor degeneration, and several epidemiologic studies have suggested that long-term history of exposure to light may have some impact on the incidence of age-related macular degeneration. In humans environmental lighting conditions have a deleterious effect on the progression of the AMD and retinitis pigmentosa (Thomas et al. 2007; Taylor et al. 1992).

Saffron has shown retinal neuroprotective properties in animal models of retinal degenerative disorders. Saffron exhibited protective effect against light-induced damage of photoreceptors, by maintaining both morphology and function. Saffron-treated animals exhibited both the preservation of the photoreceptor layer and reduction of photoreceptor death, when exposed to bright continuous light (Maccarone et al 2008).

Saffron for its regulatory mechanism on cellular targets (Natoli et al, 2010) and for possessing diverse biological properties beneficial to AMD, is a superior ingredient for an ideal ocular nutritional supplement. Crocetin, the aglycon form of the carotenoid crocin, significantly inhibited photoreceptor degeneration and retinal dysfunction in in vitro and in vivo tests. In one experiment crocetin protected against retinal damage by inhibiting an increase in caspase-3 and -9 activities after retinal damage by tunicamycin or hydrogen peroxide (Yamauchi et al. 2010).

Based on the recent research saffron activates mechanisms of self-defense and self-repair in the retina of the eye protecting it against oxidative damage. Saffron can restore some of the lost vision, and then can stabilize retina against further degeneration, which is the classic cause of development and progression of AMD.  According to ‘The Vision Centre’ -funded by the Australian Research Council: “…the golden culinary herb [saffron] can both protect and reverse the course of sight degeneration…..The herb saffron may hold one of the keys to preventing the loss of sight in old age – and may even help to improve vision…..”

According to a recent study (Marki et al, 2013) saffron prevented selenite-induced cataract formation in Wistar rats, possibly through the reinforcement of antioxidant status, reduction of the intensity of lipid peroxidation, protection of the sulfhydryl groups, and inhibition of proteolysis of the lens. These findings highlight the anticataractogenic potential of saffron by virtue of its antioxidant property.

 

Resveratrol for eye health and macular degeneration:

Current search suggest that resveratrol supplementation could offer the potential for modulating the risks in development and progression of AMD and cataracts.

Results from a recent study suggested the potential use of resveratrol as a therapeutic agent to prevent light-induced retinal degeneration (Kubota et al. 2010; Kubota et al. 2009).

In another study resveratrol has shown strong protective effects against oxysterol-induced cell death and VEGF secretion. Because drusen lesions contain numerous types of lipid including esterified and unesterified cholesterol, the pathogenesis of AMD might have some similarities with atherosclerosis. The pro-oxidative environmental conditions of eye favour the spontaneous cholesterol oxidation into oxysterols in RPE cells triggering cytotoxic, pro-inflammatory,pro-oxidative, and pro-angiogenic activities responsible for AMD lesions. Oxysterols can induce VEGF secretion on human retinal cells, implying a pro-angiogenic effects. Resveratrol has been described to down-regulate VEGF synthesis, and when used at 1 mM prevented neovascularization, which is a major complication of AMD. The authors suggested a new “therapeutic perspective” for treatment of AMD by using resveratrol (Dugas et al. 2010).

Resveratrol in both in vitro and in vivo experiments (in mouse retinas) inhibited pathological angiogenesis, induced by laser injury,by a sirtuin-independent pathway. Resveratrol inhibited the proliferation and migration of vascular endothelialcells. Abnormal angiogenesis is central to the pathophysiology of AMD. Treatment of mice with resveratrol at 45 mg/kg, delivered through subcutaneous osmotic pump, exhibited a significant protective role for resveratrol against the development and/or sustenance of CNV (Khan et al.2010). According to Dr. Rajendrar S. Apte the senior investigator of this study, “resveratrol could potentially be a preventive therapy in high-risk patients. And because it worked on existing, abnormal blood vessels in the animals, it may be a therapy that can be started after angiogenesis has already started to cause its damage.”

Resveratrol has also shown protective effects in retina via modulation of nitric oxide synthase in in vitroand in vivo oxygen-induced retinopathy models (Kim & Suh 2010).

Resveratrol due to its antiapoptotic and antioxidative properties was able to reverse significantly the loss of cell viability in ARPE-19 cell cultures. This suggested a broad beneficial effect by resveratrol against retinal diseases associated with the loss of RPE cells such as AMD (Mansoor et al 2010, PMID: 19959636). As previously mentioned, oxidative damage to RPE cells is suggested as an underlying cause of retinal damage in AMD.

It is also known that light damage to the retina accelerates retinal degeneration, and that resveratrol can prevent retinal degeneration associated with damage by light (Kubota et al. 2010).

In a recent single study on an 80-year-old man with complaints of unremitting night driving difficulty and parafoveal deposition of retinal lipofuscin, visible clearing of RPE lipofuscin was observed by using 100 mg resveratrol for 5 months. Clinically measurable and subjective improvements in vision, including self-reported night vision, dramatic improvement in contrast sensitivity function and mental function was also achieved (Richer et al. 2009).

The antioxidative, gene modifying and anti-angiogenic properties of resveratrol together with preclinical and clinical evidence, provided a strong rationale for using it in

Saffron 2020 for eye health in age-related macular degeneration (AMD) and cataracts:

 

Lutein and zeaxanthin for eye health, improving visual performance and for age-related macular degeneration

Lutein and zeaxanthin are macular carotenoids of dietary origin. Lutein is the main pigment in macula of the ye and together with its isomer zeaxanthin are also known as macular pigments or zanthophylls. There is large body of scientific evidence on eye health properties of the macular pigments (Christen et al.2008; Fletcher et al. 2008; Johnson et al. 2008; Moeller et al. 2008; Alves-Rodrigues and Shao 2004; Richer et al. 2004; Olmedilla et al. 2003; Brown et al. 1999).

Lutein is a naturally occurring pigment found in dark green leafy vegetables such as spinach, kale and collard greens. Lutein in the eye is thought to act as an antioxidant and photoprotectant. Lutein plays an important protecting role in our eyes by acting as a kind of natural sun block protecting the retina against damaging effects of too much light. Because free radicals may play a role in macular degeneration, the effect of lutein is also attributable to its antioxidant effect (Nolan et al. 2009; Johnson et al. 2008; Chucairet al. 2007; Rotstein et al. 2003; Landrum et al 1997).

It is well established that dietary intake of lutein/zeaxanthin is inversely associated with development of neovascular AMD, geographic atrophy, and large or extensive intermediate drusen (Sangiovani et al 2007; Huang et al. 2008). Experiments have shown that regular consumption of lutein supplements can increase the macular pigment density in the eye, which may potentially reduce the risk for later development of AMD (Landrum et al. 1997).

Supplementation with lutein is associated with increased macular pigment optical density (MPOD). Lutein helped stabilize visual acuity, and increased vision related quality of life in patients with AMD. No evidence of harmful side effect was found in any of these studies. (Richer et al 2007; Trieschmann et al 2007; Sartore et al. 2006). In one particular study patients ingesting lutein supplement experienced significant improvements in several objective measurements of visual function including glare recovery, contrast sensitivity, and visual acuity versus placebo. Patients experienced a 50% increase in macular pigment density relative to those on placebo pills (Richer et al. 2004).

Supplements containing lutein and zeaxanthin have promoted photoreceptor survival and differentiation in cell culture by exerting neuroprotective and antiapoptotic effect on retinal photoreceptors, which may be through the antioxidant properties of the pigments or by activation of intracellular signaling pathways. These in vitro findings support the epidemiological evidence that dietary supplements may act as factors that modulate processes implicated in AMD pathogenesis and progression (Chucair et al. 2007). In fact supplementation with lutein and zeaxanthin has led to improvements in visual function in patients with age-related macular disease (Bartlett & Eperjesie, 2005; Bartlett & Eperjesi, 2004).

Lutein may also be useful for treatment of retinitis pigmentosa, an inherited form of eye disease that causes progressive vision loss (Bahrami et al. 2006).

Despite the eye health benefits of xanthophylls, recent data suggest that dietary intake levels of these two pigments declined in Europe and the US. The average American ingests about one to two mg of lutein daily (Bartlet & Eperjesi, 2006), supporting the evidence for eye health benefits by supplementation.

An average dietary intake of greater than 6 mg/day of lutein is not uncommon, however, because lutein competes with other carotenoids for absorption it appears to be sensible to put a maximum limit of 6 mg/day lutein in a dietary supplement (Jones 2007).

The ocular health benefits of supplementation with antioxidant vitamins, zinc and carotenoids lutein/zeaxanthin are studied in patients from well-nourished developed countries, and one would expect that their beneficial effects on eye would be greater in other populations with different, likely to be less rich, dietary patterns and nutrient intake (Dherani et al.2008).

Vitamin A for eye health:

Vitamin A is a well characterised and recognized lipid soluble nutrient, which helps maintain normal vision and mucous membranes. Retinal is the active form of vitamin A in the body that is involved in photochemical reactions in the retina and is needed for normal vision, particularly for night vision, which can be affected over the years and specially in AMD. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1754.

 Vitamin B2 for eye health:

Vitamin B2, also known as riboflavin, is a water soluble vitamin that is involved in a wide variety of metabolic pathways, including the biosynthesis and catabolism of amino acids, fatty acids and carbohydrates. Riboflavin has an important role as a coenzyme in energy-yielding metabolism, and contributes to normal metabolism of iron. Riboflavin has antioxidant properties involved in protecting cellular components from oxidative damage. Riboflavin deficiency can cause opacity of the lens, burning and itching of the eyes, photophobia, and a loss of visual acuity. Riboflavin is a coenzyme that can help maintain normal vision. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1814.

 Vitamin C for eye health:

There have been many reports on eye health benefits of vitamin C and vitamin E in combination with zinc. Vitamin C is a water soluble antioxidant vitamin that helps protect DNA, proteins and lipids, also in retinal cells, from the oxidative damage caused by free radicals. Additionally, vitamin C contributes to normal energy-yielding metabolism and helps maintain physical health. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1815.

 Vitamin E for eye health:

Vitamin E is a potent biological antioxidant that is thought to have functional importance in maintaining cellular membrane integrity. Vitamin E has central role in protection against free-radical induced cellular damage. Vitamin E protects poly-unsaturated fatty acids of cells by scavenging free radicals. Dietary intake of vitamin E is known to protect DNA, protein and lipids from oxidative damage. Free radical damage has been implicated in a number of degenerative and age-related diseases including AMD and cataracts. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1816.

 Zinc for eye health:

There is established relationship between the dietary intake of zinc and normal DNA synthesis and cell division, protection of DNA, proteins and lipids from oxidative damage. Zinc is involved in maintenance of normal vitamin A metabolism, and maintenance of normal vision. “In retina and retinal pigment epithelium, there is evidence that zinc can modify photoreceptor plasma membranes, regulate the light-rhodopsin reaction, modulate synaptic transmission and serve as an antioxidant”. European Food Safety Authority (EFSA) Journal 2010; 8(10): 1819, and EFSA Journal, 2009: 7(9) 1229.

Zinc is a cofactor for the potent antioxidant enzyme superoxide dismutase, which helps to protect cellular components from oxidative damage by neutralising free radicals. Zinc is an antioxidant micronutrients and a cofactor involved in activity of more than 200 enzymes such as alcohol dehydrogenase, DNA polymerase and RNA polymerase (Bartlett & Eperjesi, 2004).

 Copper for eye health:

Dietary intake of copper contributes to protection of DNA, proteins and lipids from oxidative damage, and contributes to normal energy-yielding metabolism, iron transport, maintenance of the normal functional of the nervous system and immune system. European Food Safety Authority (EFSA) Journal 2010; 7(9): 1211, and European Food Safety Authority (EFSA) Journal 2010; 9(4): 2079

 Cataracts and role of nutrients to reduce the risks, and maintain eyesight:

Experiments have shown that free radicals mediate the formation of cataract. The major causes for cataract formation are free radicals, which are neutralized by the presence of endogenous antioxidants in the eye. Among the natural antioxidants and carotenoids vitamin C, vitamin E and lutein are well known for their anti-cataract properties.  And similarly as it was discussed with the role of antioxidant and development and progression of AMD, antioxidants can be supplemented in the diet for a better protection against free radicals and oxidative damage.  Vitamin C and vitamin E are capable of preventing lipid peroxidation, thereby preventing formation of excess free radical. It is particularly important that the combination of antioxidant vitamins such as vitamins C and E appear to have a synergistic effect on cataract prevention. In summary, there is significant inverse trends with risk of cataract and dietary intake of lutein/zeaxanthin and antioxidant vitamins.

There is a growing body of observational evidence to suggest a possible beneficial effect for lutein/zeaxanthin in delaying cataract formation and maintaining lens clarity (Christen et al. 2008; Moeller et al. 2008; Brown et al. 1999; Chasan-Taber et al. 1999)


Saffron 2020, premium natural health product for eye health:

Saffron 2020 is designed to address the above concerns for protecting retina and lens of the eye by taking advantage of the health benefits of saffron, resveratrol, lutein and other nutrients. Saffron 2020 is more particularly formulated for individuals affected by AMD or cataracts.

Saffron 2020 takes advantage of positive effects from a synergistic combination of saffron and resveratrol for providing both anti-oxidant, anti-inflammatory and gene modulation effects, and for influencing macular function in AMD and lens clarity in cataracts. The beneficial effects are enhanced by including well-documented eye health nutrients; vitamins A, B2, C and E, zinc, copper, lutein and zeaxanthin in combination with saffron and resveratrol.

Saffron 2020 has been evaluated by Health Canada and the NPN license was granted in 2012 (NPN 80030166).

Health Canada has granted the following health claims for Saffron 2020:

1. Helps to maintain eyesight in cataracts and age-related macular degeneration (AMD).

2. Helps to support eye health in cataracts and age-related

macular degeneration (AMD).

3. Helps to reduce the risk of developing cataracts.

4. Helps to improve macular pigment optical density.

5. Antioxidants for the maintenance of eye health.

6. Helps to maintain eyesight.

7. Antioxidants for the maintenance of good health.

Saffron 2020 helps maintain healthy vision and good eye health, and is recommended to individuals if they:

  • Are a healthy adult and want to maintain eye health over the years
  • Are diagnosed with age-related macular degeneration (AMD) or cataracts and want to maintain eyesight
  • Have family history of AMD or cataracts and want to protect eye health
  • Have lifestyle risk factors such as smoking
  • Have diet lacking important eye health nutrients at the required level
  • Are exposed to high levels of light from the sun or computer screens or experience eye strain

 

Saffron 2020 can improve quality of life for many millions of members of our aging society, and can lead to significant savings to the healthcare system.

 

References on eye health benefits of nutrients for macular degeneration and role of saffron in AMD:

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– Bahrami H, Melia M, Dagnelie G. (2006). Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289]. BMC Ophthalmol. 6:23

– Bartlett H, Eperjesi F. (2003). Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials. Ophthalmic Physiol Opt. 23(5):383-99.

– Bartlett H, Eperjesi F. (2004). An ideal ocular nutritional supplement? Ophthalmic Physiol Opt. 24(4):339-49.

– Bathaie S. Zahra and Mousavi S. Zeinab (2010). New Applications and Mechanisms of Action of Saffron and its Important Ingredients. Critical Reviews in Food Science and Nutrition, 50: 8, 761-786

– Brown L, Rimm EB, Seddon JM, Giovannucci EL, Chasan-Taber L, Spiegelman D, Willett WC, Hankinson SE. (1999). A prospective study of carotenoid intake and risk of cataract extraction in US men. The American Journal of Clinical Nutrition 70(4):517-524.

– Chasan-Taber L, Willett WC, Seddon JM, Stampfer MJ, Rosner B, Colditz GA, Speizer FE, Hankinson SE. (1999). A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. The American Journal of Clinical Nutrition 70(4):509-516.

– Christen WG, Liu S, Glynn RJ, Gaziano JM, Buring JE. (2008). Dietary carotenoids, vitamins C and E, and risk of cataract in women: a prospective study. Archives of Ophthalmology 126(1): 102-109.

– Chucair AJ, Rotstein NP, Sangiovanni JP, During A, Chew EY, Politi LE. (2007). Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: relation with docosahexaenoic acid. Invest Ophthalmol Vis Sci 48(11):5168-77.

– Dherani M, Murthy GV, Gupta SK, Young IS, Maraini G, Camparini M, Price GM, John N, Chakravarthy U, Fletcher (2008). Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a North Indian population. Invest Ophthalmol Vis Sci. 49(8):3328-35. doi: 10.1167/iovs.07-1202.

– Dugas B, Charbonnier S , Baarine M. (2010). Effects of oxysterols on cell viability, inflammatory cytokines, VEGF, and reactive oxygen species production on human retinal cells: cytoprotective effects and prevention of VEGF secretion by resveratrol. Eur J Nutr 49(7):435-46.

– Evans JR. (2006). Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD000254. DOI: 10.1002/14651858.CD000254.pub2.

– Falsini B, Piccardi M, Minnella A, Savastano C, Capoluongo E, Fadda A, Balestrazzi E, Maccarone R, Bisti S. (2010). Saffron Supplementation Improves Retinal Flicker Sensitivity in Early Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 51: 6118-6124.

– Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, de Jong PT, Rahu M, Seland J, Soubrane G, Tomazzoli L, Topouzis F, Vingerling JR, Vioque J. (2008). Sunlight exposure, antioxidants, and age-related macular degeneration. Archives of Ophthalmology (10): 1396-1403.

– Huang LL, Coleman HR, Kim J, de Monasterio F, Wong WT, Schleicher RL, Ferris FL 3rd, Chew EY. (2008). Oral supplementation of lutein/zeaxanthin and omega-3 long chain polyunsaturated fatty acids in persons aged 60 years or older, with or without AMD. Invest Ophthalmol Vis Sci 49(9):3864-69.

– Joseph J, Cole G, Head E, Ingram D. (2009). Nutrition, brain aging, and neurodegeneration. J Neurosci 29(41):12795-801.

– Johnson EJ, Chung HY, Caldarella SM, Snodderly DM. (2008). The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation. The American Journal of Clinical Nutrition 87(5):1521-1529.

– Laabich A, Vissvesvaran GP, Lieu KL, Murata K, McGinn TE, Manmoto CC, Sinclair JR, Karliga I, Leung DW, Fazwi A, Kubota R. (2006). Protective effect of crocin against blue light- and white light-mediated photoreceptor cell death in bovine and primate retinal primary cell culture. Invest Ophthalmol Vis Sci 47: 3156-3163.

– Khan AA, Dace DS, Ryazanov AG, Kelly J, Apte RS. (2010). Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway. Am J Pathol 177(1):481-92.

– Kim WT, Suh ES. (2010). Retinal protective effects of resveratrol via modulation of nitric oxide synthase on oxygen-induced retinopathy. Korean J Ophthalmol 24(2):108-18.

– Kubota S, Kurihara T, Ebinuma M, Kubota M, Yuki K, Sasaki M, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K. (2010). Resveratrol prevents light-induced retinal degeneration via suppressing activator protein-1 activation. Am J Pathol. 177(4):1725-31.

– Kubota S, Kurihara T, Mochimaru H, Satofuka S, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K. (2009). Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage and nuclear factor-kappaB activation. Invest Ophthalmol Vis Sci 50(7):3512-9.

– Landrum JT, Bone RA, Kilburn MD. (1997). The macular pigment: a possible role in protection from age-related macular degeneration. Adv Pharmacol 38:537-56

– Maccarone R, Di Marco S, Bisti S. (2008). Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Invest Ophthalmol Vis Sci 49: 1254-1261.

– Makri OE, Ferlemi AV, Lamari FN, Georgakopoulos CD. (2013). Saffron administration prevents selenite-induced cataractogenesis. Mol Vis. 19:1188-97.

– Mansoor S, Gupta N, Patil AJ, Estrago-Franco MF, Ramirez C, Migon R, Sapkal A, Kuppermann BD, Kenney MC. (2009). Inhibition of apoptosis in human retinal pigment epithelial cells treated with benzo(e)pyrene, a toxiccomponent of cigarette smoke. Invest Ophthalmol Vis Sci. 51(5):2601-7. doi: 10.1167/iovs.09-4121.

– Maraini G, Williams SL, Sperduto RD, Ferris FL, Milton RC, Clemons TE, Rosmini F, Ferrigno L. (2009). Effects of multivitamin/mineral supplementation on plasma levels of nutrients. Report No. 4 of the Italian-American clinical trial of nutritional supplements and age-related cataract. Ann Ist Super Sanita 45(2):119-27.

– Moeller SM, Voland R, Tinker L, Blodi BA, Klein ML, Gehrs KM, Johnson EJ, Snodderly DM, Wallace RB, Chappell RJ, Parekh N, Ritenbaugh C, Mares JA; CAREDS Study Group; Women’s Health Initiative. (2008). Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women’s Health Initiative. Archives of Ophthalmology 126(3):354-364.

– Natoli R, Zhu Y, Valter K, Bisti S, Eells J, Stone J (2010). Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina. Mol Vis 16: 1801-1822.

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