Serum miRNA modulations indicate changes in retinal morphology

BackgroundAge-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological disease...

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Main Authors: Riemke Aggio-Bruce, Ulrike Schumann, Adrian V. Cioanca, Fred K. Chen, Samuel McLenachan, Rachael C. Heath Jeffery, Shannon Das, Riccardo Natoli
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2023.1130249/full
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author Riemke Aggio-Bruce
Riemke Aggio-Bruce
Ulrike Schumann
Ulrike Schumann
Adrian V. Cioanca
Fred K. Chen
Fred K. Chen
Fred K. Chen
Fred K. Chen
Samuel McLenachan
Samuel McLenachan
Rachael C. Heath Jeffery
Rachael C. Heath Jeffery
Rachael C. Heath Jeffery
Shannon Das
Riccardo Natoli
Riccardo Natoli
author_facet Riemke Aggio-Bruce
Riemke Aggio-Bruce
Ulrike Schumann
Ulrike Schumann
Adrian V. Cioanca
Fred K. Chen
Fred K. Chen
Fred K. Chen
Fred K. Chen
Samuel McLenachan
Samuel McLenachan
Rachael C. Heath Jeffery
Rachael C. Heath Jeffery
Rachael C. Heath Jeffery
Shannon Das
Riccardo Natoli
Riccardo Natoli
author_sort Riemke Aggio-Bruce
collection DOAJ
description BackgroundAge-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.MethodsSerum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.ResultsDifferential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.ConclusionIn conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.
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spelling doaj.art-804584487caa4f2abc873926c9e1c3c82023-03-03T06:02:23ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-03-011610.3389/fnmol.2023.11302491130249Serum miRNA modulations indicate changes in retinal morphologyRiemke Aggio-Bruce0Riemke Aggio-Bruce1Ulrike Schumann2Ulrike Schumann3Adrian V. Cioanca4Fred K. Chen5Fred K. Chen6Fred K. Chen7Fred K. Chen8Samuel McLenachan9Samuel McLenachan10Rachael C. Heath Jeffery11Rachael C. Heath Jeffery12Rachael C. Heath Jeffery13Shannon Das14Riccardo Natoli15Riccardo Natoli16The John Curtin School of Medical Research, The Australian National University, Acton, ACT, AustraliaThe School of Medicine and Psychology, Acton, ACT, AustraliaThe John Curtin School of Medical Research, The Australian National University, Acton, ACT, AustraliaThe Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaThe John Curtin School of Medical Research, The Australian National University, Acton, ACT, AustraliaCentre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, AustraliaLions Eye Institute, Perth, WA, AustraliaOphthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, AustraliaCentre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, AustraliaLions Eye Institute, Perth, WA, AustraliaCentre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, AustraliaLions Eye Institute, Perth, WA, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, AustraliaThe John Curtin School of Medical Research, The Australian National University, Acton, ACT, AustraliaThe John Curtin School of Medical Research, The Australian National University, Acton, ACT, AustraliaThe School of Medicine and Psychology, Acton, ACT, AustraliaBackgroundAge-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.MethodsSerum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.ResultsDifferential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.ConclusionIn conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1130249/fullage-related macular degenerationmicroRNAdiagnosticsserum miRNAsneurodegeneration
spellingShingle Riemke Aggio-Bruce
Riemke Aggio-Bruce
Ulrike Schumann
Ulrike Schumann
Adrian V. Cioanca
Fred K. Chen
Fred K. Chen
Fred K. Chen
Fred K. Chen
Samuel McLenachan
Samuel McLenachan
Rachael C. Heath Jeffery
Rachael C. Heath Jeffery
Rachael C. Heath Jeffery
Shannon Das
Riccardo Natoli
Riccardo Natoli
Serum miRNA modulations indicate changes in retinal morphology
Frontiers in Molecular Neuroscience
age-related macular degeneration
microRNA
diagnostics
serum miRNAs
neurodegeneration
title Serum miRNA modulations indicate changes in retinal morphology
title_full Serum miRNA modulations indicate changes in retinal morphology
title_fullStr Serum miRNA modulations indicate changes in retinal morphology
title_full_unstemmed Serum miRNA modulations indicate changes in retinal morphology
title_short Serum miRNA modulations indicate changes in retinal morphology
title_sort serum mirna modulations indicate changes in retinal morphology
topic age-related macular degeneration
microRNA
diagnostics
serum miRNAs
neurodegeneration
url https://www.frontiersin.org/articles/10.3389/fnmol.2023.1130249/full
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