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Abstract
Age related macular degeneration (AMD) is the leading cause of blindness among people aged 50 and over. Retinal deposition of amyloid-β (Aβ) aggregates in AMD patients has suggested a potential link between AMD and Alzheimer's disease (AD). We have evaluated the differential retinal expression profile of miRNAs in a rat model of AMD elicited by Aβ. A serum profile of miRNAs in AMD patients has been also assessed using single TaqMan assay. Analysis of retina from rats intravitreally injected with Aβ revealed that miR-27a, miR-146a, and miR-155 were up-regulated in comparison to control rats. Seven miRNA (miR-9, miR-23a, miR-27a, miR-34a, miR-126, miR-146a, and miR-155) have been found to be dysregulated in serum of AMD patients in comparison to control group. Analysis of pathways has revealed that dysregulated miRNAs, both in the AMD animal model and in AMD patients, can target genes regulating pathways linked to neurodegeneration and inflammation, reinforcing the hypothesis that AMD is a protein misfolding disease similar to AD. In fact, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have been found to be dysregulated both in AMD and AD. In conclusion, we suggest that miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 represent potential biomarkers and new pharmacological targets for AMD.
Highlights
Age related macular degeneration (AMD) is a common eye disease and the leading cause of blindness among people aged 50 years and older
Dysregulation of miRNAs in AMD and Alzheimer’s disease (AD) has been evaluated by accessing to miR2Disease and Human microRNA Disease Database (HMDD) and through literature search (Romano et al, 2015)
We analyzed the expression of 13 miRNAs (Table 1), in retina extracts from Sprague Dawley rats subjected to intravitreal injection of Aβ oligomers
Summary
Age related macular degeneration (AMD) is a common eye disease and the leading cause of blindness among people aged 50 years and older. Injection of Aβ in the posterior chamber of animal eye induces inflammation (Howlett et al, 2011; Liu et al, 2013), apoptosis (Fisichella et al, 2016), and blood-retinal barrier (BRB) breakdown (Anderson et al, 2008) Because these data suggest that some common mechanism may link AMD and AD, we tested the hypothesis that the profile of miRNA expression in an animal model of Aβ-induced retinal damage and in patients affected by AMD might show some similarities. In the perspective of a translational approach, analysis of miRNAs may provide new insights in the pathogenic mechanisms of AMD co-shared with AD, and novel biomarkers and pharmacological targets
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