The regulatory role of microRNAs in common eye diseases: A brief review

Abstract

MicroRNAs (miRNAs) are highly conserved, small non-coding RNA molecules (∼21 nucleotides) that regulate numerous biological processes, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation, and proliferation either by mRNA degradation or translation repression. Since eye physiology requires a perfect orchestration of complex regulatory networks, an altered expression of key regulatory molecules such as miRNAs potentially leads to numerous eye disorders. In recent years, comprehensive progress has been made in demonstrating the precise roles of miRNAs, emphasizing their potential use in diagnostic and therapeutic purposes of chronic human diseases. Thus, this review explicitly illustrates the regulatory roles of miRNAs in four common eye disorders, such as cataract, glaucoma, macular degeneration, and uveitis, and their application in disease management.

Keywords: cataracts; glaucoma; macular degeneration; microRNA; uveitis.

FIGURE 1

Association of miRNAs in the pathogenesis of (A) cataract (B) glaucoma (C) macular degeneration (D) uveitis (A) The differential expression of several miRNAs strongly influences Cataractogenesis. miR-199a-5p is downregulated and targets SP1, therefore affecting the EMT of LECs. ROS is another contributing factor to the development of cataracts, and their formation is promoted by the upregulation of miR-23b, miR-22, and miR-16. Also, LECs apoptosis is another crucial biological mechanism influenced by the downregulation of miR-29b and the upregulation of miR-15 and miR-125b, which target CACNA1C, BCL2, and p53, respectively. (B) Glaucoma is characterized by the accumulation of AH in front of the eye leading to high IOP. In addition, the upregulation of miR-93, which targets NFE2L2, triggers apoptosis in GTM cells. In NTG, let-7c-5p and let-7a-5p are related to apoptosis, while the targeting of BDNF by miR-375 has been related to neurogenesis, aging, apoptosis, and autophagy. (C) In macular degeneration, the levels of angiogenesis-related factors are correlated with the upregulation of miR-17-3p, miR-17-5p, miR-23a-3p, miR-93, miR-223-3p, miR-126a, and miR-16-5p, as well as the downregulation of miR-155-5p and miR-21-3p. MiR-19 and miR-410 are significantly relevant in macular degeneration since they target multiple genes involved in processes such as nicotinate and nicotinamide metabolism, the neurodegenerative pathway, the apoptosis pathway, the VEGF pathway, the complement, and coagulation cascade pathway and retinol metabolism. (D) The pathogenesis of uveitis is related to the differential expression of several miRNAs. Underexpressed miR-182-5p in EAU mouse-derived-Th17 cells negatively regulates its development. While the upregulation of miR-146a and miR-155 was observed in PBMC, decreasing the expression of the immunosuppressive cytokine TGFβ, resulting in inflammation. The upregulation of miR-379-5p, which targets SEMA3A, is also linked to decreased B and T cell activity. MiRNAs inside a red box represent downregulation and miRNAs inside a green box represent upregulation.