Centre for Eye Research Australia (CERA) - Research Publications

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Author: Wong, Ching-Bong × End date: 2021 × Start date: 2021 ×

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    Editorial: Somatic Cell Gene Editing for Treating Diseases
    Wong, RC-B ; Huang, J ; Li, D ; Amaral, O (FRONTIERS MEDIA SA, 2021-12-23)
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    TAK1 blockade as a therapy for retinal neovascularization
    Lin, F-L ; Wang, J-H ; Chen, J ; Zhu, L ; Chuang, Y-F ; Tu, L ; Ma, C ; Lama, S ; Ling, D ; Wong, RC-B ; Hewitt, A ; Tseng, C-L ; Bui, B ; van Wijngaarden, P ; Dusting, G ; Wang, P-Y ; Liu, G-S ( 2021-01-29)
    Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other pro-inflammatory cytokines. TAK1 is also a key mediator of inflammation, innate immune responses, apoptosis and tissue homeostasis and plays an important role in physiological angiogenesis. Its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. We investigated the regulatory role of TAK1 in pathological angiogenesis in the retina. Transcriptome analysis of human retina featuring retinal neovascularization revealed enrichment of known TAK1-mediated signaling pathways. Selective inhibition of TAK1 activation by 5Z-7-oxozeaenol attenuated aberrant retinal angiogenesis in rats following oxygen-induced retinopathy. Transcriptome profiling revealed that TAK1 activation in human microvascular endothelial cells under TNFα stimulation led to increase the gene expression related to cytokines and leukocyte-endothelial interaction, mainly through nuclear factor kappa B (NFκB) signaling pathways. These results reveal that inhibition of TAK1 signaling may have therapeutic value for the treatment of pathological angiogenesis in the retina.
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    Multi-species single-cell transcriptomic analysis of ocular compartment regulons
    Gautam, P ; Hamashima, K ; Chen, Y ; Zeng, Y ; Makovoz, B ; Parikh, BH ; Lee, HY ; Lau, KA ; Su, X ; Wong, RCB ; Chan, W-K ; Li, H ; Blenkinsop, TA ; Loh, Y-H (NATURE PORTFOLIO, 2021-09-28)
    The retina is a widely profiled tissue in multiple species by single-cell RNA sequencing studies. However, integrative research of the retina across species is lacking. Here, we construct the first single-cell atlas of the human and porcine ocular compartments and study inter-species differences in the retina. In addition to that, we identify putative adult stem cells present in the iris tissue. We also create a disease map of genes involved in eye disorders across compartments of the eye. Furthermore, we probe the regulons of different cell populations, which include transcription factors and receptor-ligand interactions and reveal unique directional signalling between ocular cell types. In addition, we study conservation of regulons across vertebrates and zebrafish to identify common core factors. Here, we show perturbation of KLF7 gene expression during retinal ganglion cells differentiation and conclude that it plays a significant role in the maturation of retinal ganglion cells.