Sanie-Jahromi Fatemeh, Hoseini Seyedeh Shahla, Nowroozzadeh M Hossein
Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Heliyon. 2024 Jul 1;10(14):e33916. doi: 10.1016/j.heliyon.2024.e33916. eCollection 2024 Jul 30.
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.
In-vitro Study.
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).
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.
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.
眼内炎是一种伴有炎症的严重感染，会影响眼睛的前部和后部。通常采用覆盖多种微生物的抗生素联合治疗。然而，视网膜色素上皮（RPE）细胞极易受到玻璃体内注射治疗的损伤。本研究旨在探讨临床相关浓度的美罗培南（单独或与万古霉素联合使用）对RPE细胞活力和炎症的影响。
体外研究。
用不同浓度的美罗培南（1/4x、x和4x；[x = 16 mg/L]）、万古霉素（30 mg/L）以及美罗培南（x）加万古霉素处理第5 - 7代的RPE细胞24小时。进行形态学评估和MTT（3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐）测定以评估药物治疗引起的细胞毒性。采用实时PCR测量凋亡基因（BCL - 2和BAX）和炎症生物标志物（IL - 1β和IL - 6）的相对表达。
美罗培南（单独或与万古霉素联合使用）对RPE细胞的形态、密度和活力均无显著影响。基因表达分析证实了这些结果，表明与对照组相比，药物处理的RPE细胞中BCL - 2/BAX比值无显著变化。在所有研究浓度下，美罗培南处理均显著诱导IL - 1β的表达。此外，在x和4x浓度下，它还显著增加了IL - 6的表达，且呈剂量依赖性。然而，单独使用万古霉素或与美罗培南联合使用时未观察到这种效应。
本研究结果表明，美罗培南单独或与万古霉素联合使用均不会诱导RPE细胞毒性。美罗培南单药治疗中IL - 1β和IL - 6上调，其临床意义有待未来的体内或临床研究阐明。
