Insights into the regulatory molecules involved in glaucoma pathogenesis

Abstract

Glaucoma is an important cause of irreversible blindness, characterized by optic nerve anomalies. Increased intraocular pressure (IOP) and aging are major risk factors. Retinal ganglion cells and trabecular meshwork cells are certainly involved in the etiology of glaucoma. Glaucoma is usually a complex disease, and various genes and functions may contribute to its etiology. Among these may be genes that encode regulatory molecules. In this review, regulatory molecules including 18 transcription factors (TFs), 195 microRNAs (miRNAs), 106 long noncoding RNAs (lncRNAs), and two circular RNAs (circRNAs) that are reasonable candidates for having roles in glaucoma pathogenesis are described. The targets of the regulators are reported. Glaucomarelated features including apoptosis, stress responses, immune functions, ECM properties, IOP, and eye development are affected by the targeted genes. The targeted genes that are frequently targeted by multiple regulators most often affect apoptosis and the related features of cell death and cell survival. BCL2, CDKN1A, and TP53 are among the frequent targets of three types of glaucoma-relevant regulators, TFs, miRNAs, and lncRNAs. TP53 was itself identified as a glaucoma-relevant TF. Several of the glaucoma-relevant TFs are themselves among frequent targets of regulatory molecules, which is consistent with existence of a complex network involved in glaucoma pathogenesis.

The Molecular Mechanisms of Trabecular Meshwork Damage in POAG and Treatment Advances

“…In POAG, TMCs undergo a series of molecular and morphological alterations which lead to a gradual decrease in their cell number and IOP elevation. The increase of IOP, in turn, results in other pathological alterations that further impair cell homeostasis, leading to a vicious circle [11].…”

“…Both aberrant stiffness of TMCs and abnormal accumulation of ECM components contribute to TM fibrosis, leading to AH outflow resistance and elevated IOP [13]. During the process of POAG, the TM displays several alterations on morphologies and functions, including cell loss, increased heterogeneity of TM cellularity, increased accumulation of ECM, reduced adhesion of TMCs to ECM, formation of cross-linked actin networks, endothelial dysregulation, changes in the cytoskeleton, altered motility, reduced adhesion of TMCs to ECM, subclinical inflammation, progressive senescence and outflow impairment [11][12][13][14][15]. TM damage might trigger cross-linked proteins formation within aging tissues with malfunctioning proteolytic and ECM remodeling, as well as apoptosis and cell loss [13].…”

Multimerin-1 and cancer: a review

“…MMRN1 downregulation is associated with chemoresistance in rectal cancer [ 111 ] and radiosensitivity and associated clinical outcome in gastric cancer [ 128 ]. The mmrn1 gene is associated with glaucoma [ 129 ] and bioinformatics analyses suggest mmrn1 as a hub gene in papillary thyroid cancer [ 130 ].…”

Translocator protein 18 kDa regulates retinal neuron apoptosis and pyroptosis in glaucoma

“…LncRNAs can indirectly regulate gene expression by specifically and competitively binding to miRNAs, thereby inhibiting the effects of miRNAs on mRNAs. Changes in the expression profile of lncRNAs in the aqueous humor of glaucoma patients have been identified [ [10] , [11] , [12] , [13] ]. In addition, multiple lncRNAs are involved in the trabecular meshwork and retinal damage in glaucoma, particularly MALAT1 [ [14] , [15] , [16] ] and H19 [ 17 , 18 ], both of which regulate RGCs loss and trabecular meshwork cell damage in glaucoma via different mechanisms.…”