A Network Biology-Guided Investigation of the Long Noncoding RNAs' Role in Glaucoma

Glaucoma is a group of eye diseases characterized by progressive harm to the optic nerve that often results in loss of vision and blindness. Recent studies suggest that deregulation in the expression of a particular type of RNAs named long noncoding RNAs (lncRNAs) can impact the development of glaucoma and, hence, are promising targets for drug discovery. LncRNAs are transcripts with a length longer than 200 nucleotides that are not translated into proteins. Their extended length differentiates them from other non-coding RNAs such as microRNAs. Furthermore, lncRNAs exhibit diverse and often unpredictable regulatory functions within gene networks, unlike the well-defined gene silencing role of microRNAs. This chapter aims to discuss the role of lncRNAs in the pathogenesis of glaucoma. We will discuss and investigate lncRNAs linked to glaucoma, examine their functional regulation mechanisms in (glaucoma) gene networks, the extent of their (abnormal) expression in the disease, and their prospective as therapeutic targets. To this end, we performed lncRNA expression analysis from publicly available datasets and utilized this information to investigate their role in key pathways and biological mechanisms contributing to glaucoma progression. We employed a computational pipeline to construct glaucoma-associated lncRNA-miRNA, miRNA-TFs, gene-miRNA, protein-TF, and TF-TFs gene networks and used them to identify lncRNAs biomarkers for early diagnosis and disease progression monitoring. We identified lncRNA-enriched regulatory clusters and explored the potential of some of these lncRNA-gene clusters as targets for new therapies for glaucoma. Using this approach, we expect to give initial steps towards the elucidation of lncRNAs' role in glaucoma onset and progression.