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Abstract
The health and function of our visual system relies on accurate gene expression. While many genetic mutations are associated with visual impairment and blindness, we are just beginning to understand the complex interplay between gene regulation and retinal pathologies. MicroRNAs (miRNAs), a class of non-coding RNAs, are important regulators of gene expression that exert their function through post-transcriptional silencing of complementary mRNA targets. According to recent transcriptomic analyses, certain miRNA species are expressed in all retinal cell types, while others are cell type-specific. As miRNAs play important roles in homeostasis, cellular function, and survival of differentiated retinal cell types, their dysregulation is associated with retinal degenerative diseases. Thus, advancing our understanding of the genetic networks modulated by miRNAs is central to harnessing their potential as therapeutic agents to overcome visual impairment. In this review, we summarize the role of distinct miRNAs in specific retinal cell types, the current knowledge on their implication in inherited retinal disorders, and their potential as therapeutic agents.
Highlights
The health and function of our visual system relies on accurate gene expression
Considering that miR-182 and -183 constitutes around 70% of all cone miRNA content, it is likely that these play major roles in cone functionality, including in the modulation of outer segment maintenance
A luciferase reporter assay confirmed that miR-134 directly interacts with the cyclic AMP-response element-binding protein (Creb), a transcription factor with central roles in neuronal protection that modulates the expression of the anti-apoptotic proteins BDNF and Bcl-2
Summary
The deliberate modulation of gene expression through the use of non-coding RNAs, commonly referred to as RNA interference [14], has been extensively utilized in basic and biomedical research. ShRNAs are designed to match the sequence of specific RNA molecules, which they target and downregulate upon delivery. The production of such shRNA molecules is driven by regular promoter elements within a plasmid or a viral vector. Standard gene delivery techniques can be applied to express the shRNA of interest in target cells. This system can be used to overexpress specific miRNAs [17]. The therapeutic use of non-coding RNAs is presently growing at an accelerated pace due to increased knowledge of miRNA functions and the wide adoption of technologies that facilitate control of their expression levels in distinct retinal cell types
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