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Published on: September 13, 2016
In-vitro safety assessment of meropenem on human retinal pigment epithelium (RPE)
Fatemeh Sanie-Jahromi1, Seyedeh Shahla Hoseini1, M Hossein Nowroozzadeh1
1Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Purpose:
Endophthalmitis is a severe infection accompanied by inflammation that affects the anterior and posterior parts of the eye. It is typically treated with a combination of antibiotics that cover various microorganisms. However, retinal pigment epithelium (RPE) cells are highly susceptible to damage from intravitreal injection therapy. This study aimed to investigate the impact of clinically relevant concentrations of meropenem (alone or in combination with vancomycin) on the viability and inflammation of RPE cells.
Design:
In-vitro Study.
Methods:
RPE cells from passages 5-7 were treated with different concentrations of meropenem (1/4x, x, and 4x; [x = 16 mg/L]), vancomycin (30 mg/L), and meropenem (x) plus vancomycin for 24 h. The morphology assessment and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay were performed to evaluate cytotoxicity due to drug treatment. Real-time PCR was used to measure the relative expression of apoptotic genes (BCL-2 and BAX) and inflammation biomarkers (IL-1b and IL-6).
Results:
Meropenem (alone or in combination with vancomycin) did not have any significant effect on RPE cell morphology, density, and viability. Gene expression analysis confirmed these results, showing no significant changes in the BCL-2/BAX ratio in drug-treated RPE cells compared to controls. Treatment with meropenem significantly induced the expression of IL-1b at all studied concentrations. Additionally, at concentrations of x and 4x, it also significantly increased the expression of IL-6, which was dose-dependent. However, this effect was not observed with vancomycin alone or in combination with meropenem.
Conclusions:
The results of this study suggest that meropenem, either alone or in combination with vancomycin, does not induce RPE cytotoxicity. There was an upregulation of IL-1b and IL-6 in meropenem monotherapy, the clinical implication of which should be elucidated in future in-vivo or clinical studies.
Insights
Meropenem and vancomycin did not harm retinal pigment epithelium (RPE) cells. However, meropenem alone increased inflammation markers (IL-1b and IL-6) in RPE cells, warranting further investigation.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Endophthalmitis is a severe intraocular infection requiring prompt antibiotic treatment.
- Intravitreal antibiotic injections are standard therapy but can pose risks to ocular tissues.
- Retinal pigment epithelium (RPE) cells are crucial for retinal health and susceptible to iatrogenic damage.
Purpose of the Study:
- To evaluate the in vitro cytotoxicity of meropenem, alone and with vancomycin, on RPE cells.
- To assess the impact of these antibiotics on RPE cell viability and inflammatory responses.
- To determine the safety profile of meropenem and vancomycin combinations for potential endophthalmitis treatment.
Main Methods:
- Primary RPE cells were exposed to various concentrations of meropenem, vancomycin, or their combination for 24 hours.
- Cell viability was assessed using MTT assays, and morphology was evaluated microscopically.
- Apoptosis (BCL-2, BAX) and inflammation (IL-1b, IL-6) gene expression were quantified via real-time PCR.
Main Results:
- Meropenem and vancomycin did not significantly affect RPE cell morphology, density, or viability at tested concentrations.
- No significant changes in the BCL-2/BAX ratio were observed, indicating no drug-induced apoptosis.
- Meropenem monotherapy significantly upregulated IL-1b and, dose-dependently, IL-6 expression in RPE cells.
Conclusions:
- Meropenem and vancomycin combinations appear safe regarding RPE cell cytotoxicity.
- Meropenem monotherapy induces pro-inflammatory cytokine expression (IL-1b, IL-6) in RPE cells.
- Further in vivo and clinical studies are needed to clarify the clinical implications of meropenem-induced inflammation.
