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Inhibition of matrix metalloproteins 9 attenuated Candida albicans induced inflammation in mouse cornea
1College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan, China. chen.dong@haut.edu.cn.
Abstract:
Since the severe corneal ulceration of mouse cornea is known to occur with inflammation. As one of imperative matrix metalloproteinase, the potential roles of matrix metalloproteins 9 (MMP9) in corneal ulceration and keratitis are still unveiled caused by fungal invasion. In this study, Candida albicans (CA) inoculated wild-type KM mice cornea was used as a model pathogen in corneal inflammation. CA invasion significantly stimulated the expression of collagen IV and MMP9 detected by RT-PCR, Real-time PCR and Immunofluorescent staining in mouse cornea as soon as 6 hours post infection, and relatively decreased at 1 day post infection. For examining the role of MMP9 in fungal keratitis, the mice corneas were subconjunctivally injected MMP9 antibody or recombinant MMP9 protein 6 hours prior to CA inoculation, using rabbit IgG as control. Subconjunctival injection of recombinant MMP9 protein prior to CA inoculation enhanced, whereas MMP9 antibody attenuated corneal ulceration and inflammation, examining basement membrane, fungal load, myeloperoxidase (MPO) and proinflammatory cytokines including Macrophage inflammatory protein 2 (MIP2), Interleukin-1β (IL-1β) and Tumor necrosis factor-α (TNF-α). Inhibition of MMP9 could potentially attenuate Candida albicans induced inflammation in mouse cornea.
Insights
Matrix metalloproteinase 9 (MMP9) plays a key role in fungal keratitis. Inhibiting MMP9 can reduce inflammation and ulceration caused by Candida albicans in mouse corneas.
Area of Science:
- Ophthalmology
- Microbiology
- Immunology
Background:
- Corneal ulceration and keratitis can result from severe inflammation.
- The specific role of matrix metalloproteinase 9 (MMP9) in fungal keratitis caused by Candida albicans (CA) remains unclear.
Purpose of the Study:
- To investigate the role of MMP9 in Candida albicans-induced fungal keratitis in a mouse model.
- To determine if MMP9 inhibition can mitigate corneal inflammation and ulceration.
Main Methods:
- Wild-type KM mice were inoculated with Candida albicans (CA) to model fungal keratitis.
- Expression of collagen IV and MMP9 was analyzed using RT-PCR, Real-time PCR, and immunofluorescent staining.
- Mice received subconjunctival injections of MMP9 antibody or recombinant MMP9 protein before CA inoculation.
Main Results:
- CA infection significantly upregulated collagen IV and MMP9 expression in mouse corneas within 6 hours.
- Recombinant MMP9 protein enhanced corneal ulceration and inflammation.
- MMP9 antibody administration attenuated corneal ulceration, inflammation, fungal load, and pro-inflammatory cytokine levels (MIP2, IL-1β, TNF-α).
Conclusions:
- Matrix metalloproteinase 9 (MMP9) is involved in the inflammatory response during Candida albicans keratitis.
- Inhibiting MMP9 activity offers a potential therapeutic strategy to attenuate fungal keratitis and its associated inflammation.

