miRNA expressione profiles in retinal neurodegenerative diseases

Abstract

MicroRNAs (miRNAs) are non-coding small RNAs, which have been found to regulate gene expression at the post-transcriptional and translational levels. A lot of studies demonstrated that miRNAs regulate various cellular processes, including differentiation, development, aging, apoptosis, oncogenesis and metabolism. Moreover, dysregulation of specific miRNAs is associated with a variety of diseases, including neurodegenerative disorders. Identification of differenzial pattern expression of miRNAs could be of value for development of novel biomarkers and discovery of new pharmacological targets for human diseases. The aim of our research was to investigate miRNAs regulation in neurodegenerative diseases. Glaucoma is a progressive optic nerve neuropathy and it is one of the leading cause of blindness in the industrialized countries. Age related macular degeneration (AMD) is the leading cause of blindness among people aged 50 and over. Signs of irreversible neurodegeneration in glaucoma, AMD and Alzheimer s disease (AD), are usually evident at least a decade after onset of disease; thus early diagnosis is an urgent need in order to start effective therapy against neurodegenerative process. Identification of deregulated miRNA and associated pathways common to glaucoma, AMD and AD might help in the challenging search of biomarkers and novel therapeutic strategies. We found, from literature search, 8 deregulated miRNAs in glaucoma, 9 and 23 in AMD and AD, respectively. One miRNA was found to be commonly deregulated in glaucoma and AMD (miR-23a), two miRNA (miR-29a, miR-29b) in glaucoma and AD, and four miRNAs in AMD and AD (miR-9, miR-31, miR-21, miR-34a, miR-146a). Predicted miRNAs common to the three neurodegenerative diseases were 9 (miR-107, miR-137, miR-146a, miR-181c, miR-197, miR-21, miR-22, miR-590, miR-9), which demonstrate to be involved in the regulation of inflammation pathways. Based on prediction of miRNA and associated biochemical pathways, inflammation could represent a therapeutic target common to glaucoma, AMD and AD. Then we evaluated the differential expression profile of miRNAs in a rat model of AMD and in patients with AMD. Analysis of rat retina revealed that miR-27a, miR-146a and miR-155 are 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. Dysregulated miRNAs, both in the AMD animal model and in AMD patients, can target genes regulating pathways linked to neurodegeneration and inflammation. Our findings support the assessment of specific miRNAs as potential biomarkers and therapeutic targets in retinal neurodegenerative diseases by means of preclinical and clinical studies.