RETINAL AGING. The component of the retina which is essential for maintaining visual function and photoreceptor survival is the Retinal Pigment Epithelium (RPE).(1) The RPE provides the homeostasis of the retina, including phagocytosis, a process by which the shedding of the outer segments of photoreceptors is removed and properly disposed as waste products. It is critical that phagocytosis provide daily removal of the shedded segments to maintain vision. Phagocytosis denote a highly active lysosomal activity in the RPE of the retina. Aging of retinal results in a degression of lysosomal activity and accumulation of waste material (Lipofuscin). (2) Furthermore, age related photooxidation of the cellular membrane of the retina further damages the RPE and retinal function.
LIPOFUSCIN AND MACULAR DEGENERATION. Lipofuscin is generated through oxidative stress and a result of waste products. When the retina loses phagocytosis, there is photoreceptor degeneration.(1) Diminished phagocytosis results in increased lipofuscin accumulated in the RPE, which in turn negatively affects the RPE and photoreceptors. Lipofuscin levels also increase through oxidative stress in the retina. Accumulation of lipofuscin is an indicator of RPE atrophy and macular degeneration. As powerful antioxidants, lutein and zeaxanthin can reduce formation of lipofuscin. Zeaxanthin in particular can further help by supporting the phagocytosis removal of lipofuscin.(3,4)
The RPE contains the pigments melanin (in melanosomes) and lipofuscin. Melanin is an antioxidant pigment, whereas lipofucsin is the byproduct of waste material from photoreceptor removal and oxidative stress, which increases with dysfunction of phagocytosis. The accumulation of lipofuscin reduces the protection of melanin and increases oxidative stress of the RPE.(2)
While melanin is a powerful protector of the retina, aging affects the ability of melanin to protect the eye. Older melanosomes exposed to blue light, significantly inhibited phagocytosis - which accelerated degeneration of photoreceptors.. Therefore, the phototoxicity of melansomes increase with age. However, the antioxidant zeaxanthin has been shown to reduce the phototoxicity potential.(3)
ZEAXANTHIN HELPS PROTECTS AGAINST RETINAL DEGENERATION
(1) By reducing Phototoxicity / Photooxidation damage of retinal cellular membranes associated with aging.
(2) By supporting Phagocytosis.and the Maintenance of the RPE.
Meso zeaxanthin is the most powerful version of zeaxanthin, and is found in the central macula.
(1) Valiente-Soriano F, et al. Tracing the retina to analyze the integrity and phagocytic capacity of the retinal pigment epithelium.Sci Rep. 2020.
(2) Bonilha V.. Age and disease-related structural changes in the retinal pigment epithelium. Clin. Ophthalmol. 2008 Jun
(3) Olchawa M, et al. The effect of aging and antioxidants on photoreactivity and phototoxicity of human melanosomes; an in vitro study. Pigment Cell Melanoma Res, 2020 Jul 23.
(4) Olchawa M, et al. Zeaxanthin and α-tocopherol reduce the inhibitory effects of photodynamic stress on phagocytosis by ARPE-19 cells. Free Radic Biol Med. 2015 Dec.
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
Protective macular pigments consist of lutein, zeaxanthin and meso zeaxanthin which act as powerful lipid antioxidants as well as functioning as an anti-inflammatory in the retina. In both the retina and the brain, these pigments are readily absorbed into the cellular membranes and orient themselves perpendicular in the membrane which acts to stabilize the cellular membrane.(1) The cellular membrane is made from unsaturated fats, which are very susceptible to free radical induced oxidative damage by high energy short wave light (such as blue light). As a potent lipid antioxidants, lutein, zeaxanthin and meso zeaxanthin signifcantly boost protection of the cellular membrane, and thereby protecting cells of the retina cells and neurons in the brain.(2)
(1) Subczynski WK, et al. Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes. Arch Biochem Biophys. 2010 Dec
(2) Widomska J, et al. Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain? Foods. 2016 Mar.
(3) Neelam K, et al. Putative protective role of lutein and zeaxanthin in diabetic retinopathy. Br J Opthalmol. 2017 May
(4) Gong X, et al. Role of macular xanthophylls in prevention of common neovascular retinopathies: retinopathy of prematurity and diabetic retinopathy. Arch Biochem Biophys. 2015 Apr.
(5) Orhan C, et al. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model. J Ocul Pharmacol Ther. 2016 Nov.
(6) Binxing Li, et al. Studies on the Singlet Oxygen Scavenging Mechanism of Human Macular Pigment.Arch Biochem Biophys, 2010 Dec.
(7) Firdous AP, et al. Amelioration of radiation-induced damages in mice by carotenoid meso-zeaxanthin. Int J Radiat Biol. 2013 Mar
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