scholarly journals Dietary Supplementation with Beta-Cryptoxanthin (BCX) Protects Against Light-Induced Retinal Damage

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 126-126
Author(s):  
Deshanie Rai ◽  
Kazim Sahin ◽  
Kazim Sahin ◽  
Emre Sahin ◽  
Mehmet Tuzcu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Angiogenic Factor ◽  
Retinal Damage ◽  
Waste Products ◽  
Health Technologies ◽  
Retinal Tissue ◽  
Age Related ◽  
Markers Of Oxidative Stress

Abstract Objectives The retinal pigment epithelium (RPE) regulates the transport of nutrients and waste products to and from the retina and protects against light and oxidative stress. Structural or physiological dysfunction of RPE leads to retinal conditions such as age-related eye disease (ARED). It is well-established that artificial and natural light is an important factor in the progression of ARED as it can induce oxidative damage and photochemical lesions. Recently, the use of LED in general lighting has raised concerns regarding the effects of this light source on the RPE. The goal was to investigate whether beta-cryptoxanthin, an efficient pro-vitamin A carotenoid can exert protective effects against LED-induced RPE cell damage. Methods Rats were fed with BCX for 4 weeks at a dose of 2 and 4 mg/kg body weight followed by retinal damage by exposing the eye to bright LED light for 48 hrs. Commercially available white LED sources, which are widely used in rat housing studies was used to induce retinal damage. Animals were sacrificed at the end of the study and retinal tissue and blood samples were collected and evaluated for retinal damage and markers of oxidative stress. Results BCX supplementation significantly reduced retinal damage as demonstrated by histopathology measurements including total retinal thickness, outer nuclear layer thickness, and swelling. Similarly, markers of oxidative stress including serum and retinal tissue levels of malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase were beneficially modulated by BCX supplementation. In parallel, BCX supplementation reduced inflammatory markers (IL-1β, IL-6, NF-κB), angiogenic factor VEGF, apoptotic proteins (Caspase-3, GAP43, GFAP, NCAM, HO-1) and mitochondrial stress markers (ATF4, ATF6, Grp78, Grp97) in retinal tissue. Conclusions Our study supports that oral supplementation of BCX dose-dependently exerts a protective effect against retinal damage induced by high-intensity light in a rat model by reducing oxidative stress, inflammation, angigogenesis and protection against mitochondrial DNA damage. BCX dietary intakes and supplementation throughout all stages of life can help protect against ARED that may start early in life. Funding Sources OmniActive Health Technologies.

scholarly journals Relationship between Oxidative Stress, Circadian Rhythms, and AMD

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
María Luisa Fanjul-Moles ◽  
Germán Octavio López-Riquelme
Keyword(s):  
Oxidative Stress ◽  
Circadian Rhythms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Retinal Damage ◽  
Cell Organelles ◽  
Age Related ◽  
Exogenous Factors ◽  
The Relationship

This work reviews concepts regarding oxidative stress and the mechanisms by which endogenous and exogenous factors produce reactive oxygen species (ROS). It also surveys the relationships between oxidative stress, circadian rhythms, and retinal damage in humans, particularly those related to light and photodamage. In the first section, the production of ROS by different cell organelles and biomolecules and the antioxidant mechanisms that antagonize this damage are reviewed. The second section includes a brief review of circadian clocks and their relationship with the cellular redox state. In the third part of this work, the relationship between retinal damage and ROS is described. The last part of this work focuses on retinal degenerative pathology, age-related macular degeneration, and the relationships between this pathology, ROS, and light. Finally, the possible interactions between the retinal pigment epithelium (RPE), circadian rhythms, and this pathology are discussed.

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 PGC-1α Protects RPE Cells of the Aging Retina against Oxidative Stress-Induced Degeneration through the Regulation of Senescence and Mitochondrial Quality Control. The Significance for AMD Pathogenesis

2018 ◽  
Vol 19 (8) ◽  
pp. 2317 ◽  
Author(s):  
Kai Kaarniranta ◽  
Jakub Kajdanek ◽  
Jan Morawiec ◽  
Elzbieta Pawlowska ◽  
Janusz Blasiak
Keyword(s):  
Oxidative Stress ◽  
Cellular Senescence ◽  
Mitochondrial Biogenesis ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Sirtuin 1 ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related

PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator of many genes involved in energy management and mitochondrial biogenesis. PGC-1α expression is associated with cellular senescence, organismal aging, and many age-related diseases, including AMD (age-related macular degeneration), an important global issue concerning vision loss. We and others have developed a model of AMD pathogenesis, in which stress-induced senescence of retinal pigment epithelium (RPE) cells leads to AMD-related pathological changes. PGC-1α can decrease oxidative stress, a key factor of AMD pathogenesis related to senescence, through upregulation of antioxidant enzymes and DNA damage response. PGC-1α is an important regulator of VEGF (vascular endothelial growth factor), which is targeted in the therapy of wet AMD, the most devastating form of AMD. Dysfunction of mitochondria induces cellular senescence associated with AMD pathogenesis. PGC-1α can improve mitochondrial biogenesis and negatively regulate senescence, although this function of PGC-1α in AMD needs further studies. Post-translational modifications of PGC-1α by AMPK (AMP kinase) and SIRT1 (sirtuin 1) are crucial for its activation and important in AMD pathogenesis.

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 Oxidative stress-mediated TXNIP loss causes RPE dysfunction

2019 ◽  
Vol 51 (10) ◽  
pp. 1-13 ◽  
Author(s):  
Min Ji Cho ◽  
Sung-Jin Yoon ◽  
Wooil Kim ◽  
Jongjin Park ◽  
Jangwook Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Common Factor ◽  
Age Related Macular Degeneration ◽  
Autophagic Flux ◽  
Blood Retinal Barrier ◽  
Rpe Cells ◽  
Age Related

Abstract The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood–retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.

scholarly journals Oxidative stress alters transcript localization of disease-causing genes in the retinal pigment epithelium

2021 ◽  
Author(s):  
Tadeusz J Kaczynski ◽  
Elizabeth D Au ◽  
Michael H Farkas
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Nuclear Retention ◽  
Age Related

Nuclear retention is a mechanism whereby RNA transcripts are held in the nucleus to maintain a proper nuclear-to-cytoplasmic balance or as a stockpile for use in responding to stimuli. Many mechanisms are employed to determine whether transcripts are retained or exported to the cytoplasm, though the extent to which tissue- or cell-type, stressors, or disease pathogenesis affect this process remains unclear. As the most biochemically active tissue in the body, the retina must mitigate endogenous and exogenous stressors to maintain cell health and tissue function. Oxidative stress, believed to contribute to the pathogenesis, or progression, of age-related macular degeneration (AMD) and inherited retinal dystrophies (IRDs), is produced both internally from biochemical processes, as well as externally from environmental insult. To evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), we performed poly-A RNA sequencing on nuclear and cytoplasmic fractions from induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide, as well as untreated controls. Under normal conditions, the number of mRNA transcripts retained in the nucleus exceeded that found in studies of other tissues. Further, the nuclear-to-cytoplasmic ratio of transcripts is altered following oxidative stress, as is the retention of genes associated with AMD, IRDs, and those important for RPE physiology. These results provide a retention catalog of all expressed mRNA in iPSC-RPE under normal conditions and after exposure to hydrogen peroxide, offering insight into one of the potential roles oxidative stress plays in the progression of visual disorders.

scholarly journals Different Doses of β-Cryptoxanthin May Secure the Retina from Photooxidative Injury Resulted from Common LED Sources

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Cemal Orhan ◽  
Mehmet Tuzcu ◽  
Hasan Gencoglu ◽  
Emre Sahin ◽  
Nurhan Sahin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Light Emitting Diode ◽  
Outer Nuclear Layer ◽  
Age Related Macular Degeneration ◽  
Heme Oxygenase 1 ◽  
Antioxidant Enzyme Activities ◽  
Potential Candidate ◽  
Retinal Damage ◽  
Retinal Tissue ◽  
Age Related

Retinal damage associated with loss of photoreceptors is a hallmark of eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Potent nutritional antioxidants were previously shown to abate the degenerative process in AMD. β-Cryptoxanthin (BCX) is an essential dietary carotenoid with antioxidant, anti-inflammatory, and provitamin A activity. It is a potential candidate for developing intervention strategies to delay the development/progression of AMD. In the current study, the effect of a novel, highly purified BCX oral formulation on the rat retinal damage model was evaluated. Rats were fed with BCX for four weeks at the doses of 2 and 4 mg/kg body weight in the form of highly bioavailable oil suspension, followed by retinal damage by exposing to the bright light-emitting diode (LED) light (750 lux) for 48 hrs. Animals were sacrificed after 48 hours, and eyes and blood samples were collected and analyzed. BCX supplementations (2 and 4 mg/kg) showed improvements in the visual condition as demonstrated by histopathology of the retina and measured parameters such as total retinal thickness and outer nuclear layer thickness. BCX supplementation helped reduce the burden of oxidative stress as seen by decreased serum and retinal tissue levels of malondialdehyde (MDA) and restored the antioxidant enzyme activities in BCX groups. Further, BCX supplementation modulated inflammatory markers (IL-1β, IL-6, and NF-κB), apoptotic proteins (Bax, Bcl-2, caspase 3), growth proteins and factors (GAP43, VEGF), glial and neuronal proteins (GFAP, NCAM), and heme oxygenase-1 (HO-1), along with the mitochondrial stress markers (ATF4, ATF6, Grp78, Grp94) in the rat retinal tissue. This study indicates that oral supplementation of BCX exerts a protective effect on light-induced retinal damage in the rats via reducing oxidative stress and inflammation, also protected against mitochondrial DNA damage and cellular death.

scholarly journals Cell Therapy for Retinal Dystrophies: From Cell Suspension Formulation to Complex Retinal Tissue Bioengineering

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Karim Ben M’Barek ◽  
Christelle Monville
Keyword(s):  
Cell Therapy ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Future Research ◽  
Therapeutic Effects ◽  
Primary Defect ◽  
Retinal Tissue ◽  
Age Related

Retinal degeneration is an irreversible phenomenon caused by various disease conditions including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). During the course of these diseases, photoreceptors (PRs) are susceptible to degeneration due to their malfunctions or to a primary dysfunction of the retinal pigment epithelium (RPE). Once lost, these cells could not be endogenously regenerated in humans, and cell therapy to replace the lost cells is one of the promising strategies to recover vision. Depending on the nature of the primary defect and the stage of the disease, RPE cells, PRs, or both might be transplanted to achieve therapeutic effects. We describe in this review the current knowledge and recent progress to develop such approaches. The different cell sources proposed for cell therapy including human pluripotent stem cells are presented with their advantages and limits. Another critical aspect described herein is the pharmaceutical formulation of the end product to be delivered into the eye of patients. Finally, we also outline the future research directions in order to develop a complex multilayered retinal tissue for end-stage patients.

scholarly journals Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone)

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tomomi Masuda ◽  
Masamitsu Shimazawa ◽  
Hideaki Hara
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Apoptotic Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Free Radical Scavenger ◽  
Age Related Macular Degeneration ◽  
Radical Scavenger ◽  
Retinal Diseases ◽  
Age Related

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document