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.
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