scholarly journals Identification of Diagnostic Biomarkers and Their Correlation with Immune Infiltration in Age-Related Macular Degeneration

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1079
Author(s):  
Yuyang Zeng ◽  
Xiujuan Yin ◽  
Changzheng Chen ◽  
Yiqiao Xing
Keyword(s):  
Macular Degeneration ◽  
T Cell Activation ◽  
Immune Cells ◽  
Cell Activation ◽  
Macrophage Polarization ◽  
Predictive Performance ◽  
Age Related Macular Degeneration ◽  
Functional Enrichment ◽  
Diagnostic Biomarker ◽  
Age Related

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of the central retina, with no suitable biomarkers for early diagnosis and treatment. This study aimed to find potential diagnostic biomarker candidates for AMD and investigate their immune-related roles in this pathology. Weight gene correlation analysis was first performed based on data from the Gene Expression Omnibus database and 20 hub genes were identified. The functional enrichment analyses showed that the innate immune response, inflammatory response, and complement activation were key pathways associated with AMD. Complement C1s (C1S), adrenomedullin (ADM), and immediate early response 5 like (IER5L) were identified as the crucial genes with favorable diagnostic values for AMD by using LASSO analysis and multiple logistic regression. Furthermore, a 3-gene model was constructed and proved to be of good diagnostic and predictive performance for AMD (AUC = 0.785, 0.840, and 0.810 in training, test, and validation set, respectively). Finally, CIBERSORT was used to evaluate the infiltration of immune cells in AMD tissues. The results showed that the NK cells, CD4 memory T cell activation, and macrophage polarization may be involved in the AMD process. C1S, ADM, and IER5L were correlated with the infiltration of the above immune cells. In conclusion, our study suggests that C1S, ADM, and IER5L are promising diagnostic biomarker candidates for AMD and may regulate the infiltration of immune cells in the occurrence and progression of AMD.

scholarly journals Macrophage polarization in the maculae of age-related macular degeneration: A pilot study

2011 ◽  
Vol 61 (9) ◽  
pp. 528-535 ◽  
Author(s):  
Xiaoguang Cao ◽  
Defen Shen ◽  
Mrinali M. Patel ◽  
Jingsheng Tuo ◽  
T. Mark Johnson ◽  
...  
Keyword(s):  
Pilot Study ◽  
Macular Degeneration ◽  
Macrophage Polarization ◽  
Age Related Macular Degeneration ◽  
Age Related

Examining the added value of microperimetry and low luminance deficit for predicting progression in age-related macular degeneration

2020 ◽  
pp. bjophthalmol-2020-315935
Author(s):  
Zhichao Wu ◽  
Chi D Luu ◽  
Lauren AB Hodgson ◽  
Emily Caruso ◽  
Fred K Chen ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Characteristic Curve ◽  
Population Level ◽  
Predictive Performance ◽  
Age Related Macular Degeneration ◽  
Added Value ◽  
Fundus Photography ◽  
Individual Level ◽  
Age Related ◽  
Low Luminance

PurposeTo examine the added predictive value of microperimetric sensitivity and low luminance deficit (LLD; difference between photopic and low luminance visual acuity (VA)) to information from colour fundus photography (CFP) for progression to late age-related macular degeneration (AMD) in individuals with bilateral large drusen.Methods140 participants with bilateral large drusen underwent baseline microperimetry testing, VA measurements and CFP. They were then reviewed at 6-monthly intervals to 36 months, to determine late AMD progression. Microperimetry pointwise sensitivity SD (PSD), LLD and the presence of pigmentary abnormalities on CFPs were determined. Predictive models based on these parameters were developed and examined.ResultsBaseline microperimetry PSD and presence of pigmentary abnormalities were both significantly associated with time to develop late AMD (p≤0.004), but LLD was not (p=0.471). The area under the receiver operating characteristic curve (AUC) for discriminating between eyes that progressed to late AMD based on models using microperimetry PSD (AUC=0.68) and LLD (AUC=0.58) alone was significantly lower than that based on CFP grading for the presence of pigmentary abnormalities (AUC=0.80; both p<0.005). Addition of microperimetry and/or LLD information to a model that included CFP grading did not result in any improvement in its predictive performance (AUC=0.80 for all; all p≥0.66).ConclusionsWhile microperimetry, but not LLD, was significantly and independently associated with AMD progression at the population level, this study observed that both measures were suboptimal at predicting progression at the individual level when compared to conventional CFP grading and their addition to the latter did not improve predictive performance.

scholarly journals Leukocyte Integrin Antagonists as a Novel Option to Treat Dry Age-Related Macular Degeneration

2021 ◽  
Vol 11 ◽  
Author(s):  
Monica Baiula ◽  
Alberto Caligiana ◽  
Andrea Bedini ◽  
Junwei Zhao ◽  
Federica Santino ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Adhesion Molecules ◽  
Immune Cells ◽  
Age Related Macular Degeneration ◽  
Mrna Levels ◽  
Rpe Cells ◽  
Age Related ◽  
Dry Amd ◽  
Integrin Antagonists ◽  
Apoptosis And Necrosis

Age-related macular degeneration (AMD) is a complex multifactorial degenerative disease that leads to irreversible blindness. AMD affects the macula, the central part of the retina responsible for sharp central vision. Retinal pigment epithelium (RPE) is the main cellular type affected in dry AMD. RPE cells form a monolayer between the choroid and the neuroretina and are in close functional relationship with photoreceptors; moreover, RPE cells are part of the blood retina barrier that is disrupted in ocular diseases such as AMD. During ocular inflammation lymphocytes and macrophages are recruited, contact RPE and produce pro-inflammatory cytokines, which play an important role in AMD pathogenesis. The interaction between RPE and immune cells is mediated by leukocyte integrins, heterodimeric transmembrane receptors, and adhesion molecules, including VCAM-1 and ICAM-1. Within this frame, this study aimed to characterize RPE-leukocytes interaction and to investigate any potentially beneficial effects induced by integrin antagonists (DS-70, MN27 and SR714), developed in previous studies. ARPE-19 cells were co-cultured for different incubation times with Jurkat cells and apoptosis and necrosis levels were analyzed by flow cytometry. Moreover, we measured the mRNA levels of the pro-inflammatory cytokine IL-1β and the expression of adhesion molecules VCAM-1 and ICAM-1. We found that RPE-lymphocyte interaction increased apoptosis and necrosis levels in RPE cells and the expression of IL-1β. This interaction was mediated by the binding of α4β1 and αLβ2 integrins to VCAM-1 and ICAM-1, respectively. The blockade of RPE-lymphocyte interaction with blocking antibodies highlighted the pivotal role played by integrins. Therefore, α4β1 and αLβ2 integrin antagonists were employed to disrupt RPE-lymphocyte crosstalk. Small molecule integrin antagonists proved to be effective in reducing RPE cell death and expression of IL-1β, demonstrating that integrin antagonists could protect RPE cells from detrimental effects induced by the interaction with immune cells recruited to the retina. Overall, the leukocyte integrin antagonists employed in the present study may represent a novel opportunity to develop new drugs to fight dry AMD.

scholarly journals Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Judith Lechner ◽  
Mei Chen ◽  
Ruth E. Hogg ◽  
Levente Toth ◽  
Giuliana Silvestri ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Immune Cells ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Integrated bioinformatics analysis of aberrantly methylated-differentially expressed genes and pathways in age-related macular degeneration

2020 ◽  
Author(s):  
Yinchen Shen ◽  
Mo Li ◽  
Kun Liu ◽  
Xiaoyin Xu ◽  
Shaopin Zhu ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Differentially Expressed Genes ◽  
Age Related Macular Degeneration ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Ppi Networks ◽  
Age Related ◽  
Differentially Methylated Genes ◽  
Low Expression

Abstract Background: Age-related macular degeneration (AMD) represents the leading cause of visual impairment in the aging population. The goal of this study was to identify aberrantly methylated-differentially expressed genes (MDEGs) in AMD and explore the involved pathways by integrated bioinformatic analysis. Methods: Data of expression profiling GSE29801 and methylation profiling GSE102952 were obtained from the Gene Expression Omnibus database. We analyzed differentially methylated genes and differentially expressed genes in R software. Functional enrichment and protein–protein interaction (PPI) network analysis were performed using R package and Search Tool for the Retrieval of Interacting Genes online database. Hub genes were identified using Cytoscape. Results: 827 and 592 genes showed high and low expression, respectively, in GSE29801; 4117 hyper-methylated genes and 511 hypo-methylated genes were detected in GSE102952. After overlapping, we categorized 153 genes as hyper-methylated, low-expression genes (Hyper-LGs) and 24 genes as hypo-methylated, high-expression genes (Hypo-HGs). Four Hyper-LGs ( CKB , PPP3CA , TGFB2 , SOCS2 ) overlapped with AMD risk genes in Public Health Genomics and Precision Health Knowledge Base. KEGG pathway enrichment analysis indicated Hypo-HGs were enriched in the calcium signaling pathway, whereas Hyper-LGs were enriched in sphingolipid metabolism. In GO analysis, Hypo-HGs were enriched in fibroblast migration, membrane raft, coenzyme binding, etc. Hyper-LGs were enriched in mRNA transport, nuclear speck, DNA binding, etc. In PPI networks analysis, 23 nodes and 2 edges were established from Hypo-HGs, and 151 nodes and 73 edges were established from Hyper-LGs. Hub genes ( DHX9 , MAPT , PAX6 ) showed the greatest overlap. Conclusion: This study revealed potentially aberrantly MDEGs and pathways in AMD, which may improve the understanding of this disease.

Age related macular degeneration (ARMD) – pathophysiological and clinical features and therapeutic concepts

2001 ◽  
Vol 58 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ursula Körner-Stiefbold
Keyword(s):  
Macular Degeneration ◽  
Clinical Features ◽  
Altersbedingte Makuladegeneration ◽  
Age Related Macular Degeneration ◽  
Genetische Faktoren ◽  
Age Related ◽  
Therapeutic Concepts

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.

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