Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

Abstract

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.

Carbon Nanofibers versus Silver Nanoparticles: Time-Dependent Cytotoxicity, Proliferation, and Gene Expression

“…The activation of these two genes has been reported to be associated with defense mechanisms against stressors in human skin cells during photoaging as protective oxidative activity against UVA radiation [ 52 , 53 , 54 , 55 ]. The CNFs also increased the expression of the genes involved in the synthesis of glycoproteins such as cadherin 1 ( CDH1 ) and fibrillin ( FBN ), which are essential in the morphogenesis and development of normal tissue by connecting cells with each other [ 56 , 57 ]. The COL4A1 gene, which is abundant in the dermis, and the MMP1 gene, which is involved in the breakdown of the extracellular matrix in normal physiological processes, were also up-regulated after exposure of keratinocytes to CNFs for 24 h. The up-regulation of four of these eight genes ( FN1, TGFB1, CAT and CDH1 ) has also been observed in other CBNs such as multilayer GO [ 48 ].…”

Identification of the potential biological target molecules related to primary open-angle glaucoma

“…Injury related to elevated IOP is mainly manifested as the occurrence of TM degeneration [ 43 ]. TM is a key component of the aqueous humor outflow pathway and constitutes most of the outflow resistance [ 44 ]. In POAG, a series of pathological changes occur in the TM, leading to increased outflow resistance and elevated IOP [ 45 ].…”

miRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks

“…When the above molecules undergo activation, they can induce the expression of hundreds of genes such as those related to pro-inflammatory cytokines and chemokines, cell adhesion molecules, metalloproteinases, cell cycle regulators, pro-apoptotic molecules, etc. [ 60 , 61 , 62 , 63 , 64 ]. In the case that the oxidative/inflammatory environment will be prolonged, this can chronically affect the ocular cells and tissues leading to apoptotic cell death and glaucoma ND.…”