scholarly journals Potential of Long Non-Coding RNAs in Age-Related Macular Degeneration

2021 ◽  
Vol 22 (17) ◽  
pp. 9178
Author(s):  
Janusz Blasiak ◽  
Juha M. T. Hyttinen ◽  
Joanna Szczepanska ◽  
Elzbieta Pawlowska ◽  
Kai Kaarniranta
Keyword(s):  
Macular Degeneration ◽  
Zinc Finger Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Model Systems ◽  
Protein Coding ◽  
Age Related ◽  
Non Coding Rnas

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the aging population with poorly known pathogenesis and lack of effective treatment. Age and family history are the strongest AMD risk factors, and several loci were identified to contribute to AMD. Recently, also the epigenetic profile was associated with AMD, and some long non-coding RNAs (lncRNAs) were shown to involve in AMD pathogenesis. The Vax2os1/2 (ventral anterior homeobox 2 opposite strand isoform 1) lncRNAs may modulate the balance between pro- and anti-angiogenic factors in the eye contributing to wet AMD. The stress-induced dedifferentiation of retinal pigment epithelium cells can be inhibited by the ZNF503-AS1 (zinc finger protein 503 antisense RNA 2) and LINC00167 lncRNAs. Overexpression of the PWRN2 (Prader-Willi region non-protein-coding RNA 2) lncRNA aggravated RPE cells apoptosis and mitochondrial impairment induced by oxidative stress. Several other lncRNAs were reported to exert protective or detrimental effects in AMD. However, many studies are limited to an association between lncRNA and AMD in patients or model systems with bioinformatics. Therefore, further works on lncRNAs in AMD are rational, and they should be enriched with mechanistic and clinical studies to validate conclusions obtained in high-throughput in vitro research.

scholarly journals Efficacy of Ethanol Extract ofFructus lyciiand Its Constituents Lutein/Zeaxanthin in Protecting Retinal Pigment Epithelium Cells against Oxidative Stress:In VivoandIn VitroModels of Age-Related Macular Degeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Xinrong Xu ◽  
Li Hang ◽  
Binglin Huang ◽  
Yuanhua Wei ◽  
Shizhong Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Ethanol Extract ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Fructus Lycii

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a large role in the pathogenesis of AMD. The present study was to evaluate the effects ofFructus lyciiethanol extract on AMD in mice and to investigate whether combination of lutein and zeaxanthin, two carotenoid pigments inFructus lycii, could protect human retinal pigment epithelial ARPE-19 cells treated with hydrogen peroxide (H2O2)in vitro. We found that severe sediment beneath retinal pigment epithelium and thickened Bruch membrane occurred in AMD mice. However,Fructus lyciiethanol extract improved the histopathologic changes and decreased the thickness of Bruch membrane. Furthermore, the gene and protein expression of cathepsin B and cystatin C was upregulated in AMD mice but was eliminated byFructus lyciiethanol extract. Investigationsin vitroshowed that ARPE-19 cell proliferation was suppressed by H2O2. However, lutein/zeaxanthin not only stimulated cell proliferation but also abrogated the enhanced expression of MMP-2 and TIMP-1 in H2O2-treated ARPE-19 cells. These data collectively suggested thatFructus lyciiethanol extract and its active components lutein/zeaxanthin had protective effects on AMDin vivoandin vitro, providing novel insights into the beneficial role ofFructus lyciifor AMD therapy.

Identification of Candidate Genes Responsible for Age-related Macular Degeneration using Microarray Data

2018 ◽  
Vol 9 (2) ◽  
pp. 33-60 ◽  
Author(s):  
Yuhan Hao ◽  
Gary M. Weiss ◽  
Stuart M Brown
Keyword(s):  
Feature Selection ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Microarray Dataset ◽  
Age Related Macular Degeneration ◽  
Protein Coding ◽  
Age Related ◽  
Nf Kappab ◽  
Canonical Wnt

A DNA microarray can measure the expression of thousands of genes simultaneously, and this enables us to study the molecular pathways underlying Age-related Macular Degeneration. Previous studies have not determined which genes are responsible for the process of AMD. The authors address this deficiency by applying modern data mining and machine learning feature selection algorithms to the AMD microarray dataset. In this paper four methods are utilized to perform feature selection: Naïve Bayes, Random Forest, Random Lasso, and Ensemble Feature Selection. Functional Annotation of 20 final selected genes suggests that most of them are responsible for signal transduction in an individual cell or between cells. The top seven genes, five protein-coding genes and two non-coding RNAs, are explored from their signaling pathways, functional interactions and associations with retinal pigment epithelium cells. The authors conclude that Pten/PI3K/Akt pathway, NF-kappaB pathway, JNK cascade, Non-canonical Wnt Pathway, and two biological processes of cilia are likely to play important roles in AMD pathogenesis.

Identification of Candidate Genes Responsible for Age-Related Macular Degeneration Using Microarray Data

Biotechnology ◽  
2019 ◽  
pp. 969-1001
Author(s):  
Yuhan Hao ◽  
Gary M. Weiss ◽  
Stuart M Brown
Keyword(s):  
Feature Selection ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Microarray Dataset ◽  
Age Related Macular Degeneration ◽  
Protein Coding ◽  
Age Related ◽  
Nf Kappab ◽  
Canonical Wnt

A DNA microarray can measure the expression of thousands of genes simultaneously, and this enables us to study the molecular pathways underlying Age-related Macular Degeneration. Previous studies have not determined which genes are responsible for the process of AMD. The authors address this deficiency by applying modern data mining and machine learning feature selection algorithms to the AMD microarray dataset. In this paper four methods are utilized to perform feature selection: Naïve Bayes, Random Forest, Random Lasso, and Ensemble Feature Selection. Functional Annotation of 20 final selected genes suggests that most of them are responsible for signal transduction in an individual cell or between cells. The top seven genes, five protein-coding genes and two non-coding RNAs, are explored from their signaling pathways, functional interactions and associations with retinal pigment epithelium cells. The authors conclude that Pten/PI3K/Akt pathway, NF-kappaB pathway, JNK cascade, Non-canonical Wnt Pathway, and two biological processes of cilia are likely to play important roles in AMD pathogenesis.

scholarly journals Implication of N-Methyl-d-Aspartate Receptor in Homocysteine-Induced Age-Related Macular Degeneration

2021 ◽  
Vol 22 (17) ◽  
pp. 9356
Author(s):  
Yara A. Samra ◽  
Dina Kira ◽  
Pragya Rajpurohit ◽  
Riyaz Mohamed ◽  
Leah A. Owen ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Aspartate Receptor ◽  
Age Related ◽  
Retinal Structure

Age-related macular degeneration (AMD) is a leading cause of vision loss. Elevated homocysteine (Hcy) (Hyperhomocysteinemia) (HHcy) has been reported in AMD. We previously reported that HHcy induces AMD-like features. This study suggests that N-Methyl-d-aspartate receptor (NMDAR) activation in the retinal pigment epithelium (RPE) is a mechanism for HHcy-induced AMD. Serum Hcy and cystathionine-β-synthase (CBS) were assessed by ELISA. The involvement of NMDAR in Hcy-induced AMD features was evaluated (1) in vitro using ARPE-19 cells, primary RPE isolated from HHcy mice (CBS), and mouse choroidal endothelial cells (MCEC); (2) in vivo using wild-type mice and mice deficient in RPE NMDAR (NMDARR-/-) with/without Hcy injection. Isolectin-B4, Ki67, HIF-1α, VEGF, NMDAR1, and albumin were assessed by immunofluorescence (IF), Western blot (WB), Optical coherence tomography (OCT), and fluorescein angiography (FA) to evaluate retinal structure, fluorescein leakage, and choroidal neovascularization (CNV). A neovascular AMD patient’s serum showed a significant increase in Hcy and a decrease in CBS. Hcy significantly increased HIF-1α, VEGF, and NMDAR in RPE cells, and Ki67 in MCEC. Hcy-injected WT mice showed disrupted retina and CNV. Knocking down RPE NMDAR improved retinal structure and CNV. Our findings underscore the role of RPE NMDAR in Hcy-induced AMD features; thus, NMDAR inhibition could serve as a promising therapeutic target for AMD.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals Retinal Pigment Epithelium Expressed Toll-like Receptors and Their Potential Role in Age-Related Macular Degeneration

2021 ◽  
Vol 22 (16) ◽  
pp. 8387
Author(s):  
Alexa Klettner ◽  
Johann Roider
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Current Status ◽  
Toll Like Receptors ◽  
Cell Degeneration ◽  
Age Related

(1) Background: Inflammation is a major pathomechanism in the development and progression of age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) may contribute to retinal inflammation via activation of its Toll-like receptors (TLR). TLR are pattern recognition receptors that detect the pathogen- or danger-associated molecular pattern. The involvement of TLR activation in AMD is so far not understood. (2) Methods: We performed a systematic literature research, consulting the National Library of Medicine (PubMed). (3) Results: We identified 106 studies, of which 54 were included in this review. Based on these studies, the current status of TLR in AMD, the effects of TLR in RPE activation and of the interaction of TLR activated RPE with monocytic cells are given, and the potential of TLR activation in RPE as part of the AMD development is discussed. (4) Conclusion: The activation of TLR2, -3, and -4 induces a profound pro-inflammatory response in the RPE that may contribute to (long-term) inflammation by induction of pro-inflammatory cytokines, reducing RPE function and causing RPE cell degeneration, thereby potentially constantly providing new TLR ligands, which could perpetuate and, in the long run, exacerbate the inflammatory response, which may contribute to AMD development. Furthermore, the combined activation of RPE and microglia may exacerbate neurotoxic effects.

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.

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