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Ranibizumab Modifies the Expression of Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Mononuclear
Barbara Strzalka-Mrozik1, Olga Paprzycka1, Oliwia Gruszka1
1Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland.
Background:
Age-related macular degeneration (AMD) is the leading cause of vision loss in people over 60 years of age. Despite research, the causes of AMD remain unclear. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are known to be involved in AMD development, and anti-vascular endothelial growth factor therapy has revolutionized its treatment. This study aims to analyze the changes in gene expression in MMPs and TIMPS in patients with neovascular AMD before and after three doses of ranibizumab.
Methods:
The study involved 29 patients with neovascular AMD treated with ranibizumab. Peripheral blood mononuclear cells were collected before treatment and 24 h after the third dose of ranibizumab. We assessed MMP and TIMP gene expression profiles through oligonucleotide microarrays and validated selected differential genes using RT-qPCR.
Results:
A statistically significant change in the expression of six MMP- and TIMP-related genes was observed using oligonucleotide microarray. The mRNA levels of the two genes with the most significant fold changes, MMP15 and TIMP2, were then quantified using RT-qPCR. The results confirmed a statistically significant increase in MMP15 expression and a decrease in TIMP2 levels, although this change was not statistically significant in the group before and after the third dose of ranibizumab.
Conclusion:
Ranibizumab affects the systemic expression of MMP and TIMP-related genes in patients with neovascular AMD. Results from our exploratory study suggest that MMP15, in particular, may play a role in the treatment response, but further research is necessary.
Insights
Ranibizumab treatment for age-related macular degeneration (AMD) alters matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) gene expression. MMP15 and TIMP2 levels changed, suggesting a role in treatment response.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Age-related macular degeneration (AMD) is a primary cause of vision loss in older adults, with unclear etiology.
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are implicated in AMD pathogenesis.
- Anti-vascular endothelial growth factor (anti-VEGF) therapy, like ranibizumab, has transformed AMD treatment.
Purpose of the Study:
- To investigate changes in MMP and TIMP gene expression in neovascular AMD patients receiving ranibizumab.
- To analyze systemic gene expression profiles before and after ranibizumab treatment.
Main Methods:
- Gene expression profiling of MMPs and TIMPs in peripheral blood mononuclear cells from 29 neovascular AMD patients.
- Sample collection before treatment and 24 hours after the third ranibizumab dose.
- Oligonucleotide microarrays for initial screening and RT-qPCR for validation of key genes (MMP15, TIMP2).
Main Results:
- Oligonucleotide microarrays revealed statistically significant changes in six MMP/TIMP-related genes.
- RT-qPCR confirmed a significant increase in MMP15 mRNA levels.
- A decrease in TIMP2 levels was observed, though not statistically significant after the third ranibizumab dose.
Conclusions:
- Ranibizumab influences systemic MMP and TIMP gene expression in neovascular AMD patients.
- MMP15 may be a potential biomarker for treatment response to ranibizumab.
- Further research is warranted to elucidate the role of MMP15 in AMD treatment outcomes.
