Age Related Macular Degeneration (AMD) is characterized by retinal inflammation and oxidative stress. Chronic degeneration of the retina is related to the unbated toxic pathologies of these stressors. Lab research, using human retinal pigmented epithelium cells, indicates that the combination of Vitamin D and Meso Zeaxanthin, may provide value to early stage AMD.(1)
(1) Lazzara F, et al. Effects of Vitamin D 3 and Meso-Zeaxanthin on Human Retinal Pigmented Epithelial Cells in Three Integrated in vitro Paradigms of Age-Related Macular Degeneration. Front Phramacol. 2021 Nov.
Lycium Barbarum (LB), also known as wolfberry, has been shown to provide powerful anti-aging effects. Significantly, long term feeding of LB in lab animals have shown increased longevity, eye (retina) support, including age-related macular degeneration (AMD), support liver health and boost of intestinal health and immunity.(1)
INCREASING MEAN LIFESPAN
PRESERVING RETINA FUNCTION
PROMOTES INTESTINE HEALTH / IMMUNE RESPONSE
(1) Ding Y, et al. Effects of long-term consumption of polysaccharides from the fruit of Lycium barbarum on host's health. Food Res Int. 2021 Jan.
(2) Tang R, et al. Lycium barbarum polysaccharides extend the mean lifespan of Drosophila melanogaster. Food Funct. 2019 Jul.
(3) Neelam K, et al. Fructus lycii: A Natural Dietary Supplement for Amelioration of Retinal Diseases. Nutrients. 2021 Jan.
(4) Ding Y, et al. Modulating effects of polysaccharides from the fruits of Lycium barbarum on the immune response and gut microbiota in cyclophosphamide-treated mice.
(5) Ding Y, et al. Modulating effects of polysaccharides from the fruits of Lycium barbarum on the immune response and gut microbiota in cyclophosphamide-treated mice. Food Funct. 2019 Jun.
(6) Liu R, et al. Protective effect of Lycium barbarum polysaccharide on di-(2-ethylhexyl) phthalate-induced toxicity in rat liver. Environ Sci Pollut Res Intl. 2021. Jan.
(7) Wang H, et al. Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against alcohol-induced oxidative damage involves Nrf2 signaling. Food Sci Nutr. 2020 Oct..
Neurodegenerative diseases of the retina are mostly attributable to oxidative stress and inflammation.(1) Diseases of the retina target the retinal epithelial cells, and photoreceptors. Photoreceptors are the processing centers in the retina, and are the primary area of vision. The retina has the highest metabolic rate of any tissue in the body. Furthermore, the retina must endure oxidative stress from chronic exposure to light, which will damage the retina. In addition, retina degeneration is associated with inflammation. The result is that with age, the retina becomes damaged, and blindness is the end effect in older people.
AGE RELATED MACULAR DEGENERATION. Degeneration of retinal cells (photoreceptor and retinal pigment epitheilium (RPE) cells) by oxidative stress and inflammation is responsible for age-related macular degeneration (AMD).
(1) Oxidative Stress - NrFT2. Cellular Transcription Factor for Endogenous Antioxidant Protective Factors
Carnosic Acid is an electrophilic antioxidant which crosses the blood brain barrier. Carnoisc acid is a potent activator of Nrf2, a transcription factor that causes the increased production of endogenous antioxidants. Additionally, carnoisc acid is unqiue in that it does not deplete endogenous levels of glutathionine, the key cellular antioxidant, unlike other antioxidants.(2) In a study of high intensity lighting on photooxidative damage of the retina, adding carnoisc acid to AREDS ingredients greatly increased protection of retina vs AREDS alone.(3)
Protects the eye and retina in multiple ways. First, lycium bararum protects the photreceptor cells from light-induced retina damage by activating Nrf2.(4)
2) Inflammation - NLRP3 inflammasome activation is involed in the pathogenesis of AMD.
C3G is considered the most important anthocyanin in maintaining health of the retina. Recently, research indicates that cyanidin-3-glucoside (C3G) has potent anti-inflammation properties and may inhibit inflammasome damage to retinal epithelium cells.(5) C3G further reduces oxidative stress of the retina, and light induced retinal degeneration, by activating Nrf2 endogenous levels.(6)
(1) Rohowetz RJ, et al, Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina. Int J Mol Sci. 2018 Oct
(2) Rezaie T, et al. Protective effect of carnosic acid, a pro-electrophilic compound, in models of oxidative stress and light-induced retinal degeneration. Invest Ophthalmol Vis Sci. 2012 Nov
(3) Wong P, et al, Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration. Mol Vis. 2017 Oct
(4) Tang L, et al. Antioxidant effects of Lycium barbarum polysaccharides on photoreceptor degeneration in the light-exposed mouse retina. Biomed Pharmacother. 2018 Jul
(5) Jin X, et al. Cyanidin-3-glucoside Alleviates 4-Hydroxyhexenal-Induced NLRP3 Inflammasome Activation via JNK-c-Jun/AP-1 Pathway in Human Retinal Pigment Epithelial Cells. J Immunol Res. 2018
(6) Wang Y, et al. Cyanidin-3-glucoside and its phenolic acid metabolites attenuate visible light-induced retinal degeneration in vivo via activation of Nrf2/HO-1 pathway and NF-κB suppression. Mol Nutr Food Res. 2016 Jul
It has been well studied that the carotenoids lutein and zeaxanthin play an important role in preserving eye function by directly acting as antioxidants. However, new research indicates that these powerhouses go one important step further. This is through the activation the Nfr2 antioxidant defense network.
Nrf2 is a latent protein in the cell, that when activated, becomes a powerful transcription factor that turn on the Antioxidant Response Element (ARE). ARE is the master antioxidant switch in the cell and provides overwhelming antioxidant response, including increased levels of the potent cellular protector glutathione.
LUTEIN ZEAXANTHIN and MESO ZEAXANTHIN act as both direct antioxidants and as Nrf2 activators. Significantly, this makes their protection capacity for the retina significantly greater than only acting as an antioxidant. Implications of this include more capacity to slow the aging of the eye and preserve vision with aging.
NRF2 CELLULAR PROTECTION:
(1) Frede K, et al. Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells. J Agric Food Chem. 2017 Jun 30
(2) Liu H, et al. Protective effect of lutein on ARPE-19 cells upon H2O2-induced G2/M arrest. Mol Med Rep. 2017 Jun 21.
(3) Lima VC, et al. Macular pigment in retinal health and disease. Int J Retina Vitreous. 2016 Aug
(4) Orhan C, et al. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model. Ocul Pharmocol Ther, 2016 Nov
(5) Firdous AP. et al. Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action. Pharm Biol. 2015 Jul;53(7):961-7.
(6) Zou X, et al. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. Cell Death Dis, 2014 May
Blue Light from Electronic Technology. Eye Damaging? That is the concern. Everywhere we are constantly exposed to electronic sources of blue light, including smart phones, computer displays, LED and OLED televisions and car lights. While the light emitted from a smartphone is thought to be in the visible spectrum, there is a very high amount of short wave blue light that is also emitted. LED from cars lights, especially at night, may also pose a problem for the retina. Since we are living longer and are exposed continuously to LED lights, there is real danger the retina may be irrevocably harmed.
Natural sunlight (blue light) also causes light-induced damage to the retina, but are less intense than blue light emissions from LED devices. Therefore LED lights significantly increases the potential for toxicity to the retina. (1-4)
BLUE LIGHT DAMAGES RETINA
Photoreceptors (cones and rods) in the retina provide the neuron interface to convert light to images. These photoceptors reside on the outermost parts of the retina, and are nourished and maintained by an underlying layer termed the Retinal Pigment Epithelium (RPE). Photo induced stress directly affects the health of the retina. The blue light is especially damaging, increasing oxidative stress and can lead to cellular death to either the photoreceptors or the Retinal Epithelium.
Age-Related Macular Degeneration (AMD) involves the progressive degradation of the photoreceptors and the RPE. Blue light can damage and cause cellular death of these critical structures. Oxidative stress and inflammation are believed to be key factors in the development of AMD.
NATURAL PROTECTION AGAINST DAMAGING BLUE LIGHT
Bilberry Anthocyanins. Increases Antoxidant Protection of Retina. An experimental model of retinal degeneration, produced by visible-light damage, was ameliorated by the protective antioxidant effects of bilberry anthocyanins. (11)
Sulforaphane. Most potent Nfr2 Activator.
In studies involving the Retinal Pigment Epithelium (RPE), and oxidative stress, sulforaphane was shown to significantly up regulate antioxidant protection of the RPE by activating Nrf2 and HO-1. (12)
Aging Increases Damage from Blue Light in PhotoReceptor cells. Normal protection of the photoreceptor cells and the supporting retiinal epithelium layer, is provided by the cells inherent Nrf2 antioxidant protection against oxidative stress. However, aging is known to deplete the protective Nrf2 response, leaving the retina even more susceptible to damage by oxidative insults such as blue light. Therefore, not only does blue light inherently stress the retina and may cause cellular death, but this response is greatly amplified with retinal aging.(13-14)
(1) Coleman S. LED Lights Dangerous on Roadways and Off. 2015 Jan.
(2) Renard G, et al. The dangers of blue light. True story. J Fr Ophtalmol.2016 May.
(3) Jaadane I, et al.Retinal damage induced by commercial light emitting diodes (LEDs) Free Radic Biol Med. 2015 Jul.
(4) Krigel A, et al. Light-induced retinal damage using different light sources, protocols and rat strains reveals LED phototoxicity.Neuroscience, 2016 Dec.
(5) Lima VC, et al. Macular pigment in retinal health and disease. Int J Retina Vitreous. 2016 Aug
(6) Nolan JM, et al. The impact of supplemental macular carotenoids in Alzheimer's disease: a randomized clinical trial. J Alzheimers Dis. 2015
(7) Orthan, et al. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model. Ocul Pharmacol Ther. 2016 Nov
(8) Miyake S, et al. Phase II enzyme induction by a carotenoid, lutein, in a PC12D neuronal cell line. Biochem Biophys Res Commun. 2014 Apr
(9) Zou X, et al. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. Cell Death Dis. 2014 May
(10) Kamoshita M, et al. Lutein acts via multiple antioxidant pathways in the photo-stressed retina. Sci Rep. 2016 Jul.
(11) Wang Y, et al. Retinoprotective Effects of Bilberry Anthocyanins via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms in a Visible Light-Induced Retinal Degeneration Model in Pigmented Rabbits. Molecules. 2015 Dec
(12) Ye L, et al, Sulforaphane enhances the ability of human retinal pigment epithelial cell against oxidative stress, and its effect on gene expression profile evaluated by microarray analysis. Oxid Med Cell Longev, 2013