Abstract
MicroRNAs (miRNAs), a class of non-coding RNAs, are essential key players in the control of biological processes in both physiological and pathological conditions. miRNAs play important roles in fine tuning the expression of many genes, which often have roles in common molecular networks. miRNA dysregulation thus renders cells vulnerable to aberrant fluctuations in genes, resulting in degenerative diseases. The retinal pigment epithelium (RPE) is a monolayer of polarized pigmented epithelial cells that resides between the light-sensitive photoreceptors (PR) and the choriocapillaris. The demanding physiological functions of RPE cells require precise gene regulation for the maintenance of retinal homeostasis under stress conditions and the preservation of vision. Thus far, our understanding of how miRNAs function in the homeostasis and maintenance of the RPE has been poorly addressed, and advancing our knowledge is central to harnessing their potential as therapeutic agents to counteract visual impairment. This review focuses on the emerging roles of miRNAs in the function and health of the RPE and on the future exploration of miRNA-based therapeutic approaches to counteract blinding diseases.
Highlights
In vertebrates, the retinal pigment epithelium (RPE) originates from the dorsal portion of the optic cup, while the retina and the optic stalk develop from the distal/ventral portion (Amram et al, 2017)
Retinal–blood barrier (Simo et al, 2010); supports the isomerization of all-trans-retinal to 11-cis-retinal, the visual chromophore required for photoreceptor excitability (Strauss, 2005); protects from oxidative stress (Strauss, 2005); secretes growth factors that help to maintain the structural integrity of photoreceptors and choriocapillaris endothelium (Strauss, 2005; Mazzoni et al, 2014); establishes ocular immune privilege by expressing immunosuppressive factors (Ao et al, 2018); and is critical in the continuous renewal of the photoreceptors outer segments (POS), which are regularly shed by phagocytosis, to rebuild light-sensitive outer segments from the base of the photoreceptors (Mazzoni et al, 2014)
Due to the significant activity of microRNAs in modulating essential biological processes by targeting networks of functionally correlated genes, it is unsurprising that miRNAs have emerged as indispensable components of these molecular networks in the RPE (Soundara Pandi et al, 2013; Greene et al, 2014)
Summary
The RPE originates from the dorsal portion of the optic cup, while the retina and the optic stalk develop from the distal/ventral portion (Amram et al, 2017). In this context, supporting these observations, miR-204−/− mice showed a reduced efflux of K+ transport, which accumulates in the RPE and induces cell swelling and alteration of subretinal space (Zhang et al, 2019). Preliminary evidence for the role of miRNA in phagocytosis was reported by Murad et al (2014) showing that inhibition of miR-184 results in the upregulation of Ezrin gene and causes downregulation of the phagocytosis in ARPE19 cells, altering RPE homeostasis.
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