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Age-related macular degeneration (AMD) remains the leading cause of blindness in elderly people, but the pathophysiology of this disease is still largely unknown. We investigated the systemic expression of angiogenesis-regulating growth factors and selected miRNAs known to regulate angiogenesis in AMD patients. We also focused on possible correlations of their expression with the presence of CFH Y402H or ARMS A69S risk variants. A total of 354 AMD patients and 121 controls were enrolled in this study. The levels of angiogenesis-regulating factors were analyzed in plasma samples using Luminex technology. The expression of selected miRNAs was analyzed in peripheral blood plasma using real-time qPCR. The genetic analysis was performed with an Illumina NextSeq500 system. AMD was an independent factor associated with lower levels of angiogenin (β = -0.29, p < 0.001), endostatin (β = -0.18, p < 0.001), FGF-basic (β = -0.18, p < 0.001), PlGF (β = -0.24, p < 0.001), miRNA-21-3p (β = -0.13, p = 0.01) and miRNA-155-5p (β = -0.16, p = 0.002); and with higher levels of FGF-acidic (β = 0.11, p = 0.03), miRNA-23a-3p (β = 0.17, p < 0.001), miRNA-126-5p (β = 0.13, p = 0.009), miRNA-16-5p (β = 0.40, p < 0.001), miRNA-17-3p (β = 0.13, p = 0.01), miRNA-17-5p (β = 0.17, p < 0.001), miRNA-223-3p (β = 0.15, p = 0.004), and miRNA-93 (β = 0.11, p = 0.04). The expression of analyzed miRNA molecules significantly correlated with the levels of tested angiogenesis-regulating factors and clinical parameters in AMD patients, whereas such correlations were not observed in controls. We also found an association between the CFH Y402H polymorphism and miRNA profiles, whereby TT homozygotes showed evidently higher expression of miRNA-16-5p than CC homozygotes or TC heterozygotes ( p = 0.0007). Our results suggest that the balance between systemic pro- and anti-angiogenic factors and miRNAs is vital in multifactorial AMD pathogenesis.

Titel:	Associations of microRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism-An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration.
Autor/in / Beteiligte Person:	Ulańczyk, Z ; Sobuś, A ; Łuczkowska, K ; Grabowicz, A ; Mozolewska-Piotrowska, K ; Safranow, K ; Kawa, MP ; Pałucha, A ; Krawczyk, M ; Sikora, P ; Matczyńska, E ; Machaliński, B ; Machalińska, A
Link:	Zum Volltext
Zeitschrift:	International journal of molecular sciences, Jg. 20 (2019-11-15), Heft 22
Veröffentlichung:	Basel, Switzerland : MDPI, [2000-, 2019
Medientyp:	academicJournal
ISSN:	1422-0067 (electronic)
DOI:	10.3390/ijms20225750
Schlagwort:	Aged Aged, 80 and over Female Gene Frequency genetics Humans Intercellular Signaling Peptides and Proteins metabolism Macular Degeneration genetics Male Polymorphism, Single Nucleotide genetics Biomarkers blood Macular Degeneration blood MicroRNAs blood
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Int J Mol Sci] 2019 Nov 15; Vol. 20 (22). <i>Date of Electronic Publication: </i>2019 Nov 15. MeSH Terms: Biomarkers / blood ; Macular Degeneration / blood ; MicroRNAs / *blood ; Aged ; Aged, 80 and over ; Female ; Gene Frequency / genetics ; Humans ; Intercellular Signaling Peptides and Proteins / metabolism ; Macular Degeneration / genetics ; Male ; Polymorphism, Single Nucleotide / genetics References: Int J Mol Med. 2013 Oct;32(4):763-7. (PMID: 23863927) ; Med Sci Monit. 2015 Sep 14;21:2734-42. (PMID: 26366973) ; Cell. 1997 Jan 24;88(2):277-85. (PMID: 9008168) ; Clin Sci (Lond). 2017 Jul 5;131(15):1763-1780. (PMID: 28679845) ; Bioinformatics. 2009 Jul 15;25(14):1754-60. (PMID: 19451168) ; Drug Des Devel Ther. 2016 Jun 02;10:1857-67. (PMID: 27330279) ; Bioinformatics. 2014 Sep 15;30(18):2670-2. (PMID: 24867941) ; Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16227-32. 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(PMID: 25524721) Grant Information: UMO-2013/09/B/NZ7/04031 Polish National Science Center; STRATEGMED1/234261/2NCBR/2014 Polish National Centre for Research and Development; Interreg Cooperation Program V A Mecklenburg-Western Pomerania/Brandenburg/Poland for 2014-2020: "Consolidating cross-border cooperation through exchange of knowledge and skills in the field of modern diagnostic imaging methods in ophthalmology". European Union funds from the European Union Regional Development Fund Contributed Indexing: Keywords: AMD; CFH; angiogenesis; growth factors; miRNA Substance Nomenclature: 0 (Biomarkers) ; 0 (Intercellular Signaling Peptides and Proteins) ; 0 (MicroRNAs) Entry Date(s): Date Created: 20191117 Date Completed: 20200406 Latest Revision: 20200408 Update Code: 20240513 PubMed Central ID: PMC6887747

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Associations of microRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism-An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration.