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Bulk gene expression deconvolution reveals infiltration of M2 macrophages in retinal neovascularization

Citation

Wang, J-H and Kumar, S and Liu, G-S, Bulk gene expression deconvolution reveals infiltration of M2 macrophages in retinal neovascularization, Investigative Ophthalmology & Visual Science, 62, (14) Article 22. ISSN 1552-5783 (2021) [Refereed Article]


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Copyright 2021 The Authors. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

DOI: doi:10.1167/iovs.62.14.22

Abstract

Purpose: This study interrogated the transcriptional features and immune cellular landscape of the retinae of rats subjected to oxygen-induced retinopathy (OIR).

Methods: Bulk RNA sequencing was performed with retinal RNA isolated from control and OIR rats. Gene set enrichment analysis (GSEA) was undertaken to identify gene sets associated with immune responses in retinal neovascularization. Bulk gene expression deconvolution analysis by CIBERSORTx was performed to identify immune cell types involved in retinal neovascularization, followed by functional enrichment analysis of differentially expressed genes (DEGs). Protein–protein interaction analysis was performed to predict the hub genes relevant to identified immune cell types. CIBERSORTx was applied to profile immune cell types in the macula of patients with both proliferative diabetic retinopathy (PDR) and diabetic macular edema using a public RNA-seq dataset.

Results: Transcriptome analysis by GSEA revealed that the retina of OIR rats and patients with PDR is characterized by increased immunoregulatory interactions and complement cascade. Deconvolution analysis demonstrated that M2 macrophages infiltrate the retinae of OIR rats and patients with PDR. Functional enrichment analysis of DEGs in OIR rats showed that the dysregulated genes are related to leukocyte-mediated immunity and myeloid leukocyte activation. Downstream protein–protein interaction analysis revealed that several potential hub genes, including Ccl2, Itgam, and Tlr2, contribute to M2 macrophage infiltration in the ischemic retina.

Conclusions: This study highlights application of the gene expression deconvolution tool to identify immune cell types in inflammatory ocular diseases with transcriptomes, providing a new approach to assess changes in immune cell types in diseased ocular tissues.

Item Details

Item Type:Refereed Article
Keywords:retinal neovascularization, M2 macrophage, immune responses
Research Division:Biological Sciences
Research Group:Bioinformatics and computational biology
Research Field:Biological network analysis
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Kumar, S (Mr Satheesh Kumar)
UTAS Author:Liu, G-S (Associate Professor Guei-Sheung Liu)
ID Code:148620
Year Published:2021
Funding Support:National Health and Medical Research Council (1185600)
Web of Science® Times Cited:1
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-01-30
Last Modified:2022-02-24
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