Abstract
Primary open-angle glaucoma (POAG) is a progressive optic neuropathy and its damage to vision is irreversible. Therefore, early diagnosis assisted by biomarkers is essential. Although there were multiple researches on the identification of POAG biomarkers, few studies systematically revealed the transcriptome dysregulation mechanism of POAG from the perspective of pre- and post-transcription of genes. Here, we have collected multiple sets of POAG’s aqueous humor (AH) tissue transcription profiles covering long non-coding RNA (lncRNA), mRNA and mircoRNA (miRNA). Through differential expression analysis, we identified thousands of significant differentially expressed genes (DEGs) between the AH tissue of POAG and non-glaucoma. Further, the DEGs were used to construct a competing endogenous RNA (ceRNA) regulatory network and 1,653 qualified lncRNA-miRNA-mRNA regulatory units were identified. Two ceRNA regulatory subnets were identified based on the random walk algorithm and revealed to be involved in the regulation of multiple complex diseases. At the pre-transcriptional regulation level, a transcriptional regulatory network was constructed and three transcription factors (FOS, ATF4, and RELB) were identified to regulate the expression of multiple genes and participate in the regulation of T cells. Moreover, we revealed the immune desert status of AH tissue for POAG patients based on immune infiltration analysis and identified a specific AL590666.2-hsa−miR−339−5p-UROD axis can be used as a biomarker of POAG. Taken together, the identification of regulatory mechanisms and biomarkers will contribute to the individualized diagnosis and treatment for POAG.
Highlights
Glaucoma is the main cause of irreversible blindness, which includes several subtypes such as primary, secondary, angle-closure glaucoma and open-angle glaucoma (Weinreb and Khaw, 2004; Youngblood et al, 2019)
To explore the changes in gene expression of primary open-angle glaucoma (POAG) patients at the transcriptional level, the limma algorithm was used to identify genes that were significant differentially expressed in the Aqueous humor (AH) of POAG compared to non-glaucoma
We found that non-glaucoma samples and POAG samples can be distinguished and there are significant differences between the two groups (Figure 1C), indicating that the identified DEmRNAs and DElncRNAs can be used as the signature of POAG patients
Summary
Glaucoma is the main cause of irreversible blindness, which includes several subtypes such as primary, secondary, angle-closure glaucoma and open-angle glaucoma (Weinreb and Khaw, 2004; Youngblood et al, 2019). Primary open-angle glaucoma (POAG) is the most common. The clinical manifestations of POAG include optic nerve damage and loss of retinal ganglion cells, and high blood pressure and increased intraocular pressure are risk factors for POAG. Since the symptoms of POAG appear at a relatively late stage and the GEO accession number Platform. Potential Biomarkers for POAG Samples of POAG
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