Proteotranscriptomic analyses reveal distinct interferon-beta signaling pathways and therapeutic targets in choroidal neovascularization

• Published in: Frontiers in immunology Vol. 14; p. 1163739
• Main Authors: Hu, Yuxiang, Qi, Siyi, Zhuang, Hong, Zhuo, Qiao, Liang, Yu, Kong, Hongyu, Zhao, Chen, Zhang, Shujie
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.03.2023
• Subjects: Animals; choroidal neovascularization (CNV); Choroidal Neovascularization - drug therapy; immunity; Immunology; inflammation; Interferon-beta; interferon-β (IFN-β); Mice; Proteomics; proteotranscriptomics; Retina - pathology; Signal Transduction; interferon-β (IFN-β); immunity; inflammation; proteotranscriptomics; choroidal neovascularization (CNV)
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1163739

To investigate the molecular mechanism underlying the onset of choroidal neovascularization (CNV). Integrated transcriptomic and proteomic analyses of retinas in mice with laser-induced CNV were performed using RNA sequencing and tandem mass tag. In addition, the laser-treated mice received systemic interferon-β (IFN-β) therapy. Measurements of CNV lesions were acquired by the confocal analysis of stained choroidal flat mounts. The proportions of T helper 17 (Th17) cells were determined by flow cytometric analysis. A total of differentially expressed 186 genes (120 up-regulated and 66 down-regulated) and 104 proteins (73 up-regulated and 31 down-regulated) were identified. The gene ontology and KEGG pathway analyses indicated that CNV was mainly associated with immune and inflammatory responses, such as cellular response to IFN-β and Th17 cell differentiation. Moreover, the key nodes of the protein-protein interaction network mainly involved up-regulated proteins, including alpha A crystallin and fibroblast growth factor 2, and were verified by Western blotting. To confirm the changes in gene expression, real-time quantitative PCR was performed. Furthermore, levels of IFN-β in both the retina and plasma, as measured by enzyme-linked immunosorbent assay (ELISA), were significantly lower in the CNV group than in the control group. IFN-β treatment significantly reduced CNV lesion size and promoted the proliferation of Th17 cells in laser-treated mice. This study demonstrates that the occurrence of CNV might be associated with the dysfunction of immune and inflammatory processes and that IFN-β could serve as a potential therapeutic target.