scholarly journals Variability of the Transferrin Receptor 2 Gene in AMD

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Daniel Wysokinski ◽  
Janusz Blasiak ◽  
Mariola Dorecka ◽  
Marta Kowalska ◽  
Jacek Robaszkiewicz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Transferrin Receptor ◽  
Fenton Reaction ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Its Gene ◽  
Transferrin Receptor 2

Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Iron may catalyze the Fenton reaction resulting in overproduction of reactive oxygen species. Transferrin receptor 2 plays a critical role in iron homeostasis and variability in its gene may influence oxidative stress and AMD occurrence. To verify this hypothesis we assessed the association between polymorphisms of theTFR2gene and AMD. A total of 493 AMD patients and 171 matched controls were genotyped for the two polymorphisms of theTFR2gene: c.1892C>T (rs2075674) and c.−258+123T>C (rs4434553). We also assessed the modulation of some AMD risk factors by these polymorphisms. The CC and TT genotypes of the c.1892C>T were associated with AMD occurrence but the latter only in obese patients. The other polymorphism was not associated with AMD occurrence, but the CC genotype was correlated with an increasing AMD frequency in subjects withBMI<26. The TT genotype and the T allele of this polymorphism decreased AMD occurrence in subjects above 72 years, whereas the TC genotype and the C allele increased occurrence of AMD in this group. The c.1892C>T and c.−258+123T>C polymorphisms of theTRF2gene may be associated with AMD occurrence, either directly or by modulation of risk factors.

scholarly journals Polymorphism of the Transferrin Gene in Eye Diseases: Keratoconus and Fuchs Endothelial Corneal Dystrophy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Katarzyna A. Wójcik ◽  
Ewelina Synowiec ◽  
Manuel P. Jiménez-García ◽  
Anna Kaminska ◽  
Piotr Polakowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Fenton Reaction ◽  
Iron Homeostasis ◽  
Corneal Dystrophy ◽  
Eye Diseases ◽  
Blood Lymphocytes ◽  
Its Gene ◽  
Pcr Rflp ◽  
Transferrin Gene

Oxidative stress may play a role in the pathogenesis of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Iron may promote the stress by the Fenton reaction, so its homeostasis should be strictly controlled. Transferrin is essential for iron homeostasis because it transports iron from plasma into cells. The malfunction of transferrin, which may be caused by variation in its gene (TF) variation, may contribute to oxidative stress and change KC and FECD risk. To verify this hypothesis we investigated the association between three polymorphisms of theTFgene, g.3296G>A (rs8177178), g.3481A>G (rs8177179), and c.–2G>A (rs1130459), and KC and FECD occurrence. Genotyping was performed in blood lymphocytes in 216 patients with KC, 130 patients with FECD and 228 controls by PCR-RFLP. We studied also the influence of other risk factors. The A/A genotype and the A allele of the g.3296G>A polymorphism were associated with KC occurrence, while the G allele was negatively correlated with it. We observed a decrease in KC occurrence associated with the A/G genotype of the g.3481A>G polymorphism. We did not find any association between the c.–2G>A polymorphism and KC. No association was found between all three polymorphisms and FECD occurrence.

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.

Transferrin receptor levels and polymorphism of its gene in age-related macular degeneration

2015 ◽  
Vol 62 (2) ◽  
pp. 177-184 ◽  
Author(s):  
Daniel Wysokinski ◽  
Katarzyna Danisz ◽  
Elzbieta Pawlowska ◽  
Mariola Dorecka ◽  
Dorota Romaniuk ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Transferrin Receptor ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Its Gene

Saffron and retina: Neuroprotection and pharmacokinetics

2014 ◽  
Vol 31 (4-5) ◽  
pp. 355-361 ◽  
Author(s):  
SILVIA BISTI ◽  
RITA MACCARONE ◽  
BENEDETTO FALSINI
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Clinical Trial ◽  
Neuroprotective Effect ◽  
Experimental Studies ◽  
Dietary Supplementation ◽  
Complex Interaction ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
And Function

AbstractAge-related macular degeneration (AMD) is a retinal neurodegenerative disease whose development and progression are the results of a complex interaction between genetic and environmental risk factors. Both oxidative stress and chronic inflammation play a significant role in the pathogenesis of AMD. Experimental studies in rats with light-induced photoreceptors degeneration demonstrated that saffron may protect photoreceptor from retinal stress, preserving both morphology and function and probably acting as a regulator of programmed cell death, in addition to its antioxidant and anti-inflammatory properties. Recently, a randomized clinical trial showed that in patients with early AMD, dietary supplementation with saffron was able to improve significantly the retinal flicker sensitivity suggesting neuroprotective effect of the compound. Here, we examine the progress of saffron dietary supplementation both in animal model and AMD patients, and discuss the potential and safety for using dietary saffron to treat retinal degeneration.

scholarly journals Protective Effect of Melatonin against Oxidative Stress-Induced Apoptosis and Enhanced Autophagy in Human Retinal Pigment Epithelium Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Chih-Chao Chang ◽  
Tien-Yi Huang ◽  
Hsin-Yuan Chen ◽  
Tsui-Chin Huang ◽  
Li-Chun Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Cell Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Human Rpe Cells

Age-related macular degeneration (AMD) affects the retinal macula and results in loss of vision, and AMD is the primary cause of blindness and severe visual impairment among elderly people worldwide. AMD is characterized by the accumulation of drusen in the Bruch’s membrane and dysfunction of retinal pigment epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD remains unclear, and no effective treatment exists. Accumulating evidence indicates that oxidative stress plays a critical role in RPE cell degeneration and AMD. Melatonin is an antioxidant that scavenges free radicals, and it has anti-inflammatory, antitumor, and antiangiogenic effects. This study investigated the antioxidative, antiapoptotic, and autophagic effects of melatonin on oxidative damage to RPE cells. We used hydrogen peroxide (H2O2) to stimulate reactive oxygen species production to cause cell apoptosis in ARPE-19 cell lines. Our findings revealed that treatment with melatonin significantly inhibited H2O2-induced RPE cell damage, decreased the apoptotic rate, increased the mitochondrial membrane potential, and increased the autophagy effect. Furthermore, melatonin reduced the Bax/Bcl-2 ratio and the expression levels of the apoptosis-associated proteins cytochrome c and caspase 7. Additionally, melatonin upregulated the expression of the autophagy-related proteins LC3-II and Beclin-1 and downregulated the expression of p62. Thus, melatonin’s effects on autophagy and apoptosis can protect against H2O2-induced oxidative damage in human RPE cells. Melatonin may have multiple protective effects on human RPE cells against H2O2-induced oxidative damage.

scholarly journals Heterotypic interactions between transferrin receptor and transferrin receptor 2

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 2008-2014 ◽  
Author(s):  
Todd M. Vogt ◽  
Aaron D. Blackwell ◽  
Anthony M. Giannetti ◽  
Pamela J. Bjorkman ◽  
Caroline A. Enns
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Hereditary Hemochromatosis ◽  
Metabolic Labeling ◽  
Western Blots ◽  
Cellular Iron ◽  
Transferrin Receptor 2

Cellular iron uptake in most tissues occurs via endocytosis of diferric transferrin (Tf) bound to the transferrin receptor (TfR). Recently, a second transferrin receptor, transferrin receptor 2 (TfR2), has been identified and shown to play a critical role in iron metabolism. TfR2 is capable of Tf-mediated iron uptake and mutations in this gene result in a rare form of hereditary hemochromatosis unrelated to the hereditary hemochromatosis protein, HFE. Unlike TfR, TfR2 expression is not controlled by cellular iron concentrations and little information is currently available regarding the role of TfR2 in cellular iron homeostasis. To investigate the relationship between TfR and TfR2, we performed a series of in vivo and in vitro experiments using antibodies generated to each receptor. Western blots demonstrate that TfR2 protein is expressed strongest in erythroid/myeloid cell lines. Metabolic labeling studies indicate that TfR2 protein levels are approximately 20-fold lower than TfR in these cells. TfR and TfR2 have similar cellular localizations in K562 cells and coimmunoprecipitate to only a very limited extent. Western analysis of the receptors under nonreducing conditions reveals that they can form heterodimers.

scholarly journals Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 763
Author(s):  
Sara Romero-Vazquez ◽  
Víctor Llorens ◽  
Alba Soler-Boronat ◽  
Marc Figueras-Roca ◽  
Alfredo Adan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Macular Degeneration ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Low Grade ◽  
Complement Factor ◽  
Age Related ◽  
And Oxidative Stress

Age-related macular degeneration (AMD) heads the list of legal blindness among the elderly population in developed countries. Due to the complex nature of the retina and the variety of risk factors and mechanisms involved, the molecular pathways underlying AMD are not yet fully defined. Persistent low-grade inflammation and oxidative stress eventually lead to retinal pigment epithelium dysfunction and outer blood–retinal barrier (oBRB) breakdown. The identification of AMD susceptibility genes encoding complement factors, and the presence of inflammatory mediators in drusen, the hallmark deposits of AMD, supports the notion that immune-mediated processes are major drivers of AMD pathobiology. Complement factor H (FH), the main regulator of the alternative pathway of the complement system, may have a key contribution in the pathogenesis of AMD as it is able to regulate both inflammatory and oxidative stress responses in the oBRB. Indeed, genetic variants in the CFH gene account for the strongest genetic risk factors for AMD. In this review, we focus on the roles of inflammation and oxidative stress and their connection with FH and related proteins as regulators of both phenomena in the context of AMD.

scholarly journals Oxidative stress in association with risk factors for the occurrence and development of age-related macular degeneration

2008 ◽  
Vol 65 (4) ◽  
pp. 313-318 ◽  
Author(s):  
Lepsa Zoric ◽  
Natalija Kosanovic-Jakovic ◽  
Emina Colak ◽  
Aleksandra Radosavljevic ◽  
Vesna Jaksic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Age Related

<zakljucak> Niz rezultata potvrdjuje ulogu oksidativnog stresa u etiopatogenezi AMD i to bilo kao inicijalnog ili izolovanog uzrocnog faktora, ili kao dodatnog cinioca u sklopu drugih faktora rizika. Bolje poznavanje ove oblasti prosiruje mogucnosti prevencije ove, ali i drugih bolesti starijeg zivotnog doba.

Oxidative Stress, Ocular Disease and Diabetes Retinopathy

2019 ◽  
Vol 24 (40) ◽  
pp. 4726-4741 ◽  
Author(s):  
Orathai Tangvarasittichai ◽  
Surapon Tangvarasittichai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Protein Modification ◽  
Morphological Changes ◽  
Corneal Dystrophy ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Retinal Light Damage ◽  
Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

Molecular Mechanisms of Complement System Proteins and Matrix Metalloproteinases in the Pathogenesis of Age-Related Macular Degeneration

2019 ◽  
Vol 19 (10) ◽  
pp. 705-718 ◽  
Author(s):  
Naima Mansoor ◽  
Fazli Wahid ◽  
Maleeha Azam ◽  
Khadim Shah ◽  
Anneke I. den Hollander ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Macular Degeneration ◽  
Complement System ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Genetic Changes ◽  
Complement System Proteins ◽  
Age Related ◽  
Common Genetic Variants

: Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis. Common genetic variants (with a minor allele frequency of >5% in the population) near the complement genes explain 40–60% of the heritability of AMD. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH, contribute to the formation of drusen and progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are normally involved in tissue remodeling also play a critical role in the pathogenesis of AMD. MMPs are involved in the degradation of cell debris and lipid deposits beneath retina but with age their functions get affected and result in the drusen formation, succeeding to macular degeneration. In this review, AMD pathology, existing knowledge about the normal and pathological role of complement system proteins and MMPs in the eye is reviewed. The scattered data of complement system proteins, MMPs, drusenogenesis, and lipofusogenesis have been gathered and discussed in detail. This might add new dimensions to the understanding of molecular mechanisms of AMD pathophysiology and might help in finding new therapeutic options for AMD.

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