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Ashok Kumar, Sukhvinder Singh, Indu Khatri, Pawan Kumar Singh; Temporal genome-wide co-expression profiling of coding and long non-coding RNA (lncRNA) in experimental staphylococcal endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4635. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Long non-coding RNAs (lncRNA) have emerged as central regulators in numerous physiological and pathological processes, including microbial infections. However, their roles in bacterial endophthalmitis remain to be elucidated. The aim of this study is to examine lncRNA and coding RNA (mRNA) expression profiles in bacterial endophthalmitis, which could provide molecular insights in the pathobiology of this disease.
Endophthalmitis was induced in C57BL/6 mice by intravitreal injections of S. aureus. Whole genome-wide lncRNA microarray (v3) was performed in neuroretina collected at various time post infection (6, 12, 24, 48 and 72 hour) with PBS injected retina as controls. Gene ontology, pathway, and network analysis of differentially expressed lncRNA were performed to predict the functions of cis and trans target genes. The expression of highly dysregulated lncRNAs was validated by qRT-PCR. To determine the cell specificity of lncRNA expression, in vitro studies were performed using bone marrow-derived macrophages (BMDM) and neutrophils challenged with S. aureus.
Our data show altered expression of 3,212 lncRNA and 2,688 mRNA where 210 lncRNAs and 321 mRNAs were temporarily dysregulated in S. aureus endophthalmitis. Pathway analysis revealed diverse biological pathways being affected in the retina, including inflammatory responses, angiogenesis, and cellular metabolism. Using lncRNA-mRNA co-expression and correlation network analysis, 10 highly interacting pairs of lncRNA and mRNA were identified and validated. Among these, lncRNA 4933432103RIK was found to be interesting due to its proximity in potentially regulating a highly upregulated protein-coding gene aconitate decarboxylase 1 (Acod1) which interacts with classical inflammatory mediators (Ccl2, Ccl3, Ccl4, Cxcl2, IL-1β & IL-6) gene clusters. Similar to infected mouse retina, the expression of the identified lncRNAs and their potential target mRNAs were found to be highly upregulated in S. aureus challenged macrophages and neutrophils.
To our knowledge, this is the first study to report an integrated mRNA-lncRNA signature in bacterial endophthalmitis. While further investigations are needed to determine biological functions of identified lncRNA, our data may provide a useful resource for identifying novel biomarkers associated with this ocular infectious disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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