Complement-mediated inflammation and mitochondrial energy metabolism in the proteomic profile of myopic human corneas

Huang, Tianze; Wang, Yuchen; Wang, Zhonghai; Long, Qin; Y, Li; Chen, Di

doi:10.1016/j.jprot.2023.104949

Cited by 5 publications

(2 citation statements)

References 45 publications

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“…Several clusters that could be possibly associated with eye development such as photoreceptor cell development, sensory perception of light stimulus, and mitochondrial localization were suppressed in FDM. Specifically, the suppression of mitochondrial energy metabolism along with the activation complement system aligns with the findings of previous studies on myopia development [35][36][37].…”

Section: Gsea and Ppi-based Clusters Exhibited Significant Alteration...supporting

confidence: 87%

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

Kim,

Lee,

Kim

et al. 2023

Genes

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Myopia is a substantial global public health concern primarily linked to the elongation of the axial length of the eyeball. While numerous animal models have been employed to investigate myopia, the specific contributions of genetic factors and the intricate signaling pathways involved remain incompletely understood. In this study, we conducted RNA-seq analysis to explore genes and pathways in two distinct myopia-inducing mouse models: form-deprivation myopia (FDM) and lens-induced myopia (LIM). Comparative analysis with a control group revealed significant differential expression of 2362 genes in FDM and 503 genes in LIM. Gene Set Enrichment Analysis (GSEA) identified a common immune-associated pathway between LIM and FDM, with LIM exhibiting more extensive interactions. Notably, downregulation was observed in OxPhos complex III of FDM and complex IV of LIM. Subunit A of complex I was downregulated in LIM but upregulated in FDM. Additionally, complex V was upregulated in LIM but downregulated in FDM. These findings suggest a connection between alterations in energy metabolism and immune cell activation, shedding light on a novel avenue for understanding myopia’s pathophysiology. Our research underscores the necessity for a comprehensive approach to comprehending myopia development, which integrates insights from energy metabolism, oxidative stress, and immune response pathways.

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Section: Gsea and Ppi-based Clusters Exhibited Significant Alteration...supporting

confidence: 87%

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

Kim,

Lee,

Kim

et al. 2023

Genes

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“…Moreover, interleukin-18 (IL-18) and interleukin-1β (IL-1β) have been found to promote the upregulation of MMP-2 expression in various cells, and inflammatory responses can elevate the expression of these interleukins [9,10]. The research conducted by Huang et al in the field of proteomics suggests that the complement system can influence the development of myopia by affecting inflammatory responses [11]. NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) is an intracellular sensor capable of detecting various microbial patterns, endogenous danger signals, and environmental stimuli.…”

Section: Introductionmentioning

confidence: 99%

Intraperitoneal Injection of MCC950 Inhibits the Progression of Myopia in Form-Deprivation Myopic Mice

Chen,

Xiao,

Long

2023

IJMS

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Myopia, one of the most prevalent ocular diseases worldwide, is projected to affect nearly half of the global population by 2050. The main cause of myopia in most patients is axial myopia, which primarily occurs due to the elongation of the eyeball, driven by changes in the extracellular matrix (ECM) of scleral cells. Previous studies have shown that NLRP3, an important inflammatory mediator, plays a critical role in regulating the expression of MMP-2 in the sclera. This, in turn, leads to a decrease in the expression of Collagen-1, a major component of the scleral ECM, triggering the remodeling of the scleral ECM. This study aimed to investigate the effect of MCC950, an inhibitor of NLRP3, on the progression of myopia using a mouse form-deprivation myopia (FDM) model. The FDM mouse model was constructed by subjecting three-week-old C57BL/6J mice to form-deprivation. The mice were divided into experimental (n = 10/group; FDM2M, FDM4M, FDM2W, and FDM4W) and control groups (n = 5/group). The experimental groups were further categorized based on the duration of form deprivation (2 and 4 weeks, labeled as 2 and 4, respectively) and the type of injection received (MCC950 or saline, labeled as M and W, respectively). MCC950 was injected at a concentration of 50 mg/mL, with a dose of 10 mg per kilogram of body weight. Meanwhile, the saline group received the same volume of saline. Refraction and axial length measurements were performed for each eye. The expression levels of NLRP3, caspase-1, IL-1β, IL-18, MMP-2, and Collagen-1 in the sclera were assessed using immunohistochemistry and Western blotting. The intraperitoneal injection of MCC950 did not significantly affect refraction or axial length in normal mice (p > 0.05). However, in FDM mice, MCC950 attenuated the elongation of the axial length and resulted in a smaller shift towards myopia compared to the saline group (FDM4M vs. FDM4W, p = 0.03 and p < 0.05, respectively). MCC950 decreased MMP-2 expression (p < 0.05) but increased Collagen-1 expression (p < 0.05) in the experimental eyes when compared to the saline group. Within the MCC950 group, the expression of MMP-2 was increased in the experimental eyes at 4 weeks (p < 0.05), while that of Collagen-1 was decreased (p < 0.05), which is consistent with changes in refractive error. Immunohistochemical analysis yielded similar results (p < 0.05). MCC950 also reduced the expression levels of NLRP3 (p = 0.03), caspase-1 (p < 0.05), IL-1β (p < 0.05), and IL-18 (p < 0.05) in the experimental eyes compared to the saline group. Within the MCC950 group, the expression levels of NLRP3 and caspase-1 were comparable between the experimental and control eyes (p > 0.05), whereas IL-18 expression was higher in experimental eyes (p < 0.05). IL-1β expression was higher in the experimental eyes only at week 4 (p < 0.05). The intraperitoneal injection of MCC950 can inhibit the progression of myopia in FDM mice, possibly by regulating collagen remodeling in the sclera through the NLRP3-MMP-2 signaling pathway. Therefore, MCC950 holds promise as a potential therapeutic agent for controlling the progression of myopia.

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Usefulness and analytical performances of complement multiplex assay for measuring complement biomarkers in plasma

Meuleman,

Duval,

Grunenwald

et al. 2024

Clinica Chimica Acta

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Complement-mediated inflammation and mitochondrial energy metabolism in the proteomic profile of myopic human corneas

Cited by 5 publications

References 45 publications

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

Intraperitoneal Injection of MCC950 Inhibits the Progression of Myopia in Form-Deprivation Myopic Mice

Usefulness and analytical performances of complement multiplex assay for measuring complement biomarkers in plasma

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