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Updated: Aug 3, 2025
In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model
Published on: January 21, 2018
Proteotranscriptomic analyses reveal distinct interferon-beta signaling pathways and therapeutic targets in choroidal
Yuxiang Hu1, Siyi Qi1, Hong Zhuang1
1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Aim:
To investigate the molecular mechanism underlying the onset of choroidal neovascularization (CNV).
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Choroidal neovascularization (CNV) onset involves immune dysfunction. Interferon-beta (IFN-β) therapy reduced CNV lesions and modulated T helper 17 (Th17) cells, suggesting IFN-β as a potential treatment for CNV.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- The molecular mechanisms driving CNV onset require further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms underlying choroidal neovascularization (CNV).
- To explore the therapeutic potential of interferon-beta (IFN-β) in CNV.
Main Methods:
- Integrated transcriptomic and proteomic analyses were performed on laser-induced CNV mouse models.
- Interferon-beta (IFN-β) therapy was administered systemically.
- CNV lesion size, Th17 cell proportions, and IFN-β levels were quantified.
Main Results:
- Differentially expressed genes and proteins associated with immune and inflammatory responses were identified.
- IFN-β levels were lower in CNV retinas.
- IFN-β treatment significantly reduced CNV lesion size and increased Th17 cell proliferation.
Conclusions:
- CNV onset is linked to immune and inflammatory process dysfunction.
- Interferon-beta (IFN-β) shows potential as a therapeutic target for CNV.
