Related Experiment Video
Updated: Jun 26, 2026
Curcuminoid-Mediated Antimicrobial Photodynamic Therapy on a Murine Model of Oral Candidiasis
Published on: October 27, 2023
Expression of matrix metalloproteinases during experimental Candida albicans keratitis
Xiaoyong Yuan1, Bradley M Mitchell, Kirk R Wilhelmus
1Sid W. Richardson Ocular Microbiology Laboratory, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA.
Purpose:
This study was designed to investigate the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during the inception and progression of experimental keratomycosis.
Methods:
Scarified corneas of adult BALB/c mice were topically inoculated with Candida albicans strain SC5314 and monitored for disease severity. Infected and mock-infected corneas were compared at 1 day post inoculation (p.i.) with a murine gene microarray. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) determined MMP and TIMP levels at 1, 3, and 7 days p.i. for infected, mock-infected, and normal corneas. Immunostaining localized target proteins at 1 day p.i.
Results:
Eyes inoculated with C. albicans developed corneal infection with a mean clinical score of 8.2+/-0.8 at 1 day p.i. Compared to controls at 1 day p.i., MMP-8, -9, -10, -12, -13, -19, and TIMP-1 were significantly upregulated from fivefold to 375-fold by microarray and from threefold to 78-fold by real-time RT-PCR. Upregulated MMPs and TIMP-1 in the corneal epithelium and stroma of infected eyes correlated with the influx of acute inflammatory cells. Neither MMP-8 nor -13 expression was affected by mechanical trauma, but both increased >100-fold during the week after the onset of fungal keratitis. TIMP-1 expression rose from 21-fold more than controls at 1 day to 46-fold at 7 days p.i. by RT-PCR.
Conclusions:
Transcriptional and translational levels of MMP-8, -9, -13, and TIMP-1 increase during the early stages of C. albicans keratitis, confirming findings for MMP-9 and TIMP-1 in other infectious keratitis models and suggesting roles for MMP-8 and -13.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) increase during fungal keratitis. This study highlights MMP-8 and MMP-13
Area of Science:
- Ophthalmology
- Microbiology
- Molecular Biology
Background:
- Fungal keratitis is a significant cause of vision loss.
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play roles in tissue remodeling and inflammation.
- Understanding their role in fungal keratitis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression patterns of MMPs and TIMPs during experimental Candida albicans keratitis.
- To determine the temporal changes in MMP and TIMP levels during fungal infection progression.
- To correlate protein expression with inflammatory cell infiltration.
Main Methods:
- Induction of experimental keratitis in BALB/c mice using Candida albicans.
- Disease severity monitoring and clinical scoring.
- Murine gene microarray analysis at 1 day post-inoculation.
- Real-time RT-PCR for MMP and TIMP quantification at 1, 3, and 7 days post-inoculation.
- Immunostaining for protein localization.
Main Results:
- Significant upregulation of MMP-8, -9, -10, -12, -13, -19, and TIMP-1 observed in infected corneas.
- Upregulation correlated with acute inflammatory cell influx.
- MMP-8 and MMP-13 showed marked increases (>100-fold) during fungal keratitis, independent of mechanical trauma.
- TIMP-1 expression increased significantly over 7 days post-inoculation.
Conclusions:
- MMP-8, MMP-9, MMP-13, and TIMP-1 expression are elevated during early-stage Candida albicans keratitis.
- Findings confirm roles for MMP-9 and TIMP-1 in infectious keratitis.
- MMP-8 and MMP-13 emerge as potentially significant contributors to fungal keratitis pathogenesis.
