scholarly journals Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1423
Author(s):  
Maria Hernandez ◽  
Sergio Recalde ◽  
Jorge González-Zamora ◽  
Valentina Bilbao-Malavé ◽  
Manuel Sáenz de Viteri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Macular Degeneration ◽  
Oxidative Dna Damage ◽  
Retinal Pigment ◽  
Photoreceptor Cells ◽  
Age Related Macular Degeneration ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total®; N) on oxidative stress and inflammation-like induced conditions by H2O2 and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H2O2-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFNγ in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total® protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Photo-damage, photo-protection and age-related macular degeneration

2015 ◽  
Vol 14 (9) ◽  
pp. 1560-1577 ◽  
Author(s):  
Melisa D. Marquioni-Ramella ◽  
Angela M. Suburo
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Molecular Targets ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Photo Damage ◽  
Effect Of Light

The course of Age-related Macular Degeneration (AMD) is described as the effect of light (400–580 nm) on various molecular targets in photoreceptors and the retinal pigment epithelium (RPE). Photo-damage is followed by inflammation, increasing oxidative stress and, probably, unveiling new photosensitive molecules.

scholarly journals Age-Related Macular Degeneration Revisited: From Pathology and Cellular Stress to Potential Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Majda Hadziahmetovic ◽  
Goldis Malek
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Clinical Care ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) is a neurodegenerative disease of the aging retina, in which patients experience severe vision loss. Therapies available to patients are limited and are only effective in a sub-population of patients. Future comprehensive clinical care depends on identifying new therapeutic targets and adopting a multi-therapeutic approach. With this goal in mind, this review examines the fundamental concepts underlying the development and progression of AMD and re-evaluates the pathogenic pathways associated with the disease, focusing on the impact of injury at the cellular level, with the understanding that critical assessment of the literature may help pave the way to identifying disease-relevant targets. During this process, we elaborate on responses of AMD vulnerable cells, including photoreceptors, retinal pigment epithelial cells, microglia, and choroidal endothelial cells, based on in vitro and in vivo studies, to select stressful agents, and discuss current therapeutic developments in the field, targeting different aspects of AMD pathobiology.

scholarly journals Peroxisome Proliferator-Activated Receptor Expression in Murine Models and Humans with Age-related Macular Degeneration

2009 ◽  
Vol 2 (1) ◽  
pp. 141-148 ◽  
Author(s):  
Alexandra A. Herzlich ◽  
Xiaoyan Ding ◽  
Defen Shen ◽  
Robert J. Ross ◽  
Jingsheng Tuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Critical Role ◽  
Receptor Expression ◽  
Age Related Macular Degeneration ◽  
Epithelial Cell Line ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Age Related

Peroxisome proliferator-activated receptors (PPARs) play a role in oxidative stress and VEGF regulation, which are closely related to age-related macular degeneration (AMD). PPAR γ expression and its downstream molecules were examined in fat-1 mice (transgenic mice that convert n-6 to n-3 fatty acids), Ccl2-/-/Cx3cr1-/- mice (an AMD model), ARPE19 cells (a human retinal pigment epithelial cell line, RPE, a cell type with a critical role in AMD), and human eyes with and without AMD. PPAR α, β, and γ, VEGF and receptors were determined by immunohistochemistry in the mice models, humans, and ARPE19 cells. Transcripts of PPARs, VEGF, MMP-9 and HO-1 were determined by RQ-PCR. PPARs were constitutively expressed in normal neuroretina and RPE of humans and mice. PPAR γ expression was increased in fat-1 and Ccl2-/-/Cx3cr1-/- mice. VEGF was decreased in fat-1 mice but increased in Ccl2-/-/Cx3cr1-/- mice. VEGF receptors were stable. VEGF, MMP9 and HO-1 transcript levels were increased in ARPE19 cells under H2O2 - induced oxidative stress. Human AMD retinas exhibited higher PPAR γ. The findings of increased expression of PPAR γ and its downstream proteins (VEGF, MMP9, and HO-1) in H2O2-treated ARPE19 cells, Ccl2-/-/Cx3cr1-/- mice, and human AMD eyes, but decreased VEGF in fat-1 mice, suggest that PPAR γ may play a role in AMD.

scholarly journals Dietary Polyphenols in Age-Related Macular Degeneration: Protection against Oxidative Stress and Beyond

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Elzbieta Pawlowska ◽  
Joanna Szczepanska ◽  
Ali Koskela ◽  
Kai Kaarniranta ◽  
Janusz Blasiak
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Janus Kinase ◽  
Age Related Macular Degeneration ◽  
Hydroxyl Groups ◽  
Ros Scavenging ◽  
Rpe Cells ◽  
Dietary Polyphenols ◽  
Age Related

Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by degeneration and loss of photoreceptors and retinal pigment epithelium (RPE) cells with oxidative stress playing a role in its pathology. Although systematic reviews do not support the protective role of diet rich in antioxidants against AMD, dietary polyphenols (DPs) have been reported to have beneficial effects on vision. Some of them, such as quercetin and cyanidin-3-glucoside, can directly scavenge reactive oxygen species (ROS) due to the presence of two hydroxyl groups in their B ring structure. Apart from direct ROS scavenging, DPs can lower oxidative stress in several other pathways. Many DPs induce NRF2 (nuclear factor, erythroid 2-like 2) activation and expression of phase II enzymes that are under transcriptional control of this factor. DPs can inhibit A2E photooxidation in RPE cells, which is a source of oxidative stress. Anti-inflammatory action of DPs in RPE cells is associated with regulation of various interleukins and signaling pathways, including IL-6/JAK2 (Janus kinase 2)/STAT3. Some DPs can improve impaired cellular waste clearance, including AMD-specific deficient phagocytosis of the Aβ42 peptide and autophagy.

scholarly journals Protective Effects of Curcumin Ester Prodrug, Curcumin Diethyl Disuccinate against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells: Potential Therapeutic Avenues for Age-Related Macular Degeneration

2019 ◽  
Vol 20 (13) ◽  
pp. 3367 ◽  
Author(s):  
Chawanphat Muangnoi ◽  
Umar Sharif ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Pornchai Rojsitthisak ◽  
Luminita Paraoan
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Parent Drug ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Rpe Cells ◽  
Age Related ◽  
Potent Drug

Oxidative stress-induced damage to the retinal pigmented epithelium (RPE), a specialised post-mitotic monolayer that maintains retinal homeostasis, contributes to the development of age-related macular degeneration (AMD). Curcumin (Cur), a naturally occurring antioxidant, was previously shown to have the ability to protect RPE cells from oxidative stress. However, poor solubility and bioavailability makes Cur a poor therapeutic agent. As prodrug approaches can mitigate these limitations, we compared the protective properties of the Cur prodrug curcumin diethyl disuccinate (CurDD) against Cur in relation to oxidative stress induced in human ARPE-19 cells. Both CurDD and Cur significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Both drugs exerted their protective effects through the modulation of p44/42 (ERK) and the involvement of downstream molecules Bax and Bcl-2. Additionally, the expression of antioxidant enzymes HO-1 and NQO1 was also enhanced in cells treated with CurDD and Cur. In all cases, CurDD was more effective than its parent drug against oxidative stress-induced damage to ARPE-19 cells. These findings highlight CurDD as a more potent drug compared to Cur against oxidative stress and indicate that its protective effects are exerted through modulation of key apoptotic and antioxidant molecular pathways.

scholarly journals Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Janusz Blasiak ◽  
Goran Petrovski ◽  
Zoltán Veréb ◽  
Andrea Facskó ◽  
Kai Kaarniranta
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Developed Countries ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Rich

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

scholarly journals Autophagy in Age-Related Macular Degeneration: A Regulatory Mechanism of Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zi-Yuan Zhang ◽  
Xiao-Li Bao ◽  
Yun-Yi Cong ◽  
Bin Fan ◽  
Guang-Yu Li
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Therapeutic Interventions ◽  
Cell Degeneration ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of severe visual loss and irreversible blindness in the elderly population worldwide. Retinal pigment epithelial (RPE) cells are the major site of pathological alterations in AMD. They are responsible for the phagocytosis of shed photoreceptor outer segments (POSs) and clearance of cellular waste under physiological conditions. Age-related, cumulative oxidative stimuli contribute to the pathogenesis of AMD. Excessive oxidative stress induces RPE cell degeneration and incomplete digestion of POSs, leading to the continuous accumulation of cellular waste (such as lipofuscin). Autophagy is a major system of degradation of damaged or unnecessary proteins. However, degenerative RPE cells in AMD patients cannot perform autophagy sufficiently to resist oxidative damage. Increasing evidence supports the idea that enhancing the autophagic process can properly alleviate oxidative injury in AMD and protect RPE and photoreceptor cells from degeneration and death, although overactivated autophagy may lead to cell death at early stages of retinal degenerative diseases. The crosstalk among the NFE2L2, PGC-1, p62, AMPK, and PI3K/Akt/mTOR pathways may play a crucial role in improving disturbed autophagy and mitigating the progression of AMD. In this review, we discuss how autophagy prevents oxidative damage in AMD, summarize potential neuroprotective strategies for therapeutic interventions, and provide an overview of these neuroprotective mechanisms.

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