Abstract
The retina is among the most metabolically active tissues with high-energy demands. The peculiar distribution of mitochondria in cells of retinal layers is necessary to assure the appropriate energy supply for the transmission of the light signal. Photoreceptor cells (PRs), retinal pigment epithelium (RPE), and retinal ganglion cells (RGCs) present a great concentration of mitochondria, which makes them particularly sensitive to mitochondrial dysfunction. To date, visual loss has been extensively correlated to defective mitochondrial functions. Many mitochondrial diseases (MDs) show indeed neuro-ophthalmic manifestations, including retinal and optic nerve phenotypes. Moreover, abnormal mitochondrial functions are frequently found in the most common retinal pathologies, i.e., glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR), that share clinical similarities with the hereditary primary MDs. MicroRNAs (miRNAs) are established as key regulators of several developmental, physiological, and pathological processes. Dysregulated miRNA expression profiles in retinal degeneration models and in patients underline the potentiality of miRNA modulation as a possible gene/mutation-independent strategy in retinal diseases and highlight their promising role as disease predictive or prognostic biomarkers. In this review, we will summarize the current knowledge about the participation of miRNAs in both rare and common mitochondria-mediated eye diseases. Definitely, given the involvement of miRNAs in retina pathologies and therapy as well as their use as molecular biomarkers, they represent a determining target for clinical applications.
Highlights
Mitochondria are key players in different cellular processes, and their dysfunction contributes to the pathogenesis of neurodegenerative disorders (NDs), including many retinal diseases
Mitochondrial diseases (MDs) are a heterogeneous group of rare disorders caused by mutations in nuclear or mitochondrial genes that affect proteins essential for mitochondrial structure and function
The most promising miRNAs for clinical development are in bold. mtDNA, mitochondrial DNA; ATP, adenosine triphosphate; nDNA, nuclear DNA; ROS, reactive oxygen species; IOP, intraocular pressure; Mfn2, mitofusin 2; PMEDs, primary mitochondrial eye diseases; NARP, neuropathy, ataxia, and retinitis pigmentosa; EDAMDs, eye diseases associated with mitochondria dysfunctions
Summary
Mitochondria are key players in different cellular processes, and their dysfunction contributes to the pathogenesis of neurodegenerative disorders (NDs), including many retinal diseases. We will summarize the current knowledge about the involvement of miRNAs in mitochondria-mediated eye diseases, including both rare PMEDs and the most common retinal disorders, i.e., glaucoma, AMD, and DR.
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