Immunobiology · 2023
Up-regulation of scleral C5b-9 and its regulation of the NLRP3 inflammasome in a form-deprivation myopia mouse model.
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Xiao Kang, Chen Zhengyu, He Songqing, Long Qin
Аннотация
BACKGROUND: Myopia has become a major public health problem worldwide. Although the involvement of the complement system in myopia progression has been reported, the underlying mechanism has not been well established. In this study, we induced a form deprivation (FD) myopia mouse model to investigate the mechanisms.
METHODS: Both C6-knockout (KO) and wild-type (WT) mice were divided into FD and normal control (NC) groups. The FD myopia was induced in the right eyes of 24-day-old mice using a translucent balloon for 4 weeks. The left eye remained untreated and served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, and 4 weeks later under normal visual, 4 weeks after FD. Scleral transcriptome sequencing analysis was performed in in FD mice. The scleral levels of C5b-9, NLRP3, Caspase-1, IL-1β, MMP-2, and collagen I were evaluated using immunohistochemistry.
RESULTS: RNA-seq analysis showed 1058 differentially expressed genes. The GO analysis showed these genes were mainly related to the extracellular matrix, and immune response. The KEGG enrichment analysis showed that complement cascades were upregulated. Under normal visual conditions, both genotypes of mice exhibited comparable refractive error and axial length. However, after four weeks of FD, C6-KO mice showed a significantly less myopic shift (-2.28 ± 0.28 D versus -5.40 ± 1.33 D, P = 0.003), and axial shift (0.043 ± 0.032 mm versus 0.083 ± 0.026 mm, P = 0.042) in comparison to WT mice. Furthermore, the levels of C5b-9, NLRP3, caspase-1, IL-1β, and MMP-2 were found to be elevated in the deprived eyes of WT mice in comparison to their fellow eyes, whereas the extent of this increase was significantly lower in C6-KO mice.
CONCLUSIONS: Complement cascades are activated in FD myopia model. Upregulation of C5b-9 might participate in scleral remodeling during myopia progression via regulation of NLRP3 inflammasome activation.
METHODS: Both C6-knockout (KO) and wild-type (WT) mice were divided into FD and normal control (NC) groups. The FD myopia was induced in the right eyes of 24-day-old mice using a translucent balloon for 4 weeks. The left eye remained untreated and served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, and 4 weeks later under normal visual, 4 weeks after FD. Scleral transcriptome sequencing analysis was performed in in FD mice. The scleral levels of C5b-9, NLRP3, Caspase-1, IL-1β, MMP-2, and collagen I were evaluated using immunohistochemistry.
RESULTS: RNA-seq analysis showed 1058 differentially expressed genes. The GO analysis showed these genes were mainly related to the extracellular matrix, and immune response. The KEGG enrichment analysis showed that complement cascades were upregulated. Under normal visual conditions, both genotypes of mice exhibited comparable refractive error and axial length. However, after four weeks of FD, C6-KO mice showed a significantly less myopic shift (-2.28 ± 0.28 D versus -5.40 ± 1.33 D, P = 0.003), and axial shift (0.043 ± 0.032 mm versus 0.083 ± 0.026 mm, P = 0.042) in comparison to WT mice. Furthermore, the levels of C5b-9, NLRP3, caspase-1, IL-1β, and MMP-2 were found to be elevated in the deprived eyes of WT mice in comparison to their fellow eyes, whereas the extent of this increase was significantly lower in C6-KO mice.
CONCLUSIONS: Complement cascades are activated in FD myopia model. Upregulation of C5b-9 might participate in scleral remodeling during myopia progression via regulation of NLRP3 inflammasome activation.