Sanie-Jahromi Fatemeh, Ravankhah Mahdi, Shafi Khani Hossein, Razavizadegan Seyed Ahmad, Nowroozzadeh M Hossein
Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Front Pharmacol. 2025 Apr 30;16:1569703. doi: 10.3389/fphar.2025.1569703. eCollection 2025.
RPE cells serve as an experimental model for studying a retinal disease called proliferative vitreoretinopathy (PVR). The pathological background of PVR involves uncontrolled cell proliferation, increased inflammation, and enhanced epithelial-mesenchymal transition (EMT), which have been the focus of various research studies. The present study aimed to explore the effects of combination therapy using methotrexate (MTX) and dexamethasone (DEXA) on the expression of genes involved in apoptosis, inflammation and EMT in retinal pigment epithelial (RPE) cells.
Our study design comprised two sets of experiments. First, we assessed the effect of MTX serial dilutions (0.5x, x, 2x, and 4x, where x = 100 μg/mL) on RPE cells to determine the optimal concentration of MTX that promotes apoptosis-related gene expression without altering inflammatory-related gene expression. Second, we investigated the influence of MTX (at the selected dose) alone or in combination with DEXA (50 μg/mL) on apoptosis, inflammation, and EMT-related gene expression in RPE cells at the transcriptional level.
Treatment with 100 μg/mL MTX demonstrated a pro-apoptotic effect according to the expression level of and in RPE cells. The combination of MTX (100 μg/mL) and DEXA significantly reduced the expression of inflammation-related genes (), indicating a synergistic anti-inflammatory effect. However, there was no significant effect on the expression of genes related to EMT (), except for a partial neutralization of the reducing effect of MTX on and genes.
Our study highlighted the potential pro-apoptotic effect of MTX (at 100 μg/mL) on RPE cells and the synergistic anti-inflammatory impact of MTX/DEXA combination therapy. Nevertheless, this combination did not significantly affect genes associated with EMT. Further research is required to elucidate the clinical implications of these findings in the management of PVR.
视网膜色素上皮（RPE）细胞可作为研究一种名为增殖性玻璃体视网膜病变（PVR）的视网膜疾病的实验模型。PVR的病理背景涉及不受控制的细胞增殖、炎症增加以及上皮-间质转化（EMT）增强，这些一直是各种研究的重点。本研究旨在探讨甲氨蝶呤（MTX）和地塞米松（DEXA）联合治疗对视网膜色素上皮（RPE）细胞中与凋亡、炎症和EMT相关基因表达的影响。
我们的研究设计包括两组实验。首先，我们评估了MTX系列稀释液（0.5x、x、2x和4x，其中x = 100μg/mL）对RPE细胞的影响，以确定在不改变炎症相关基因表达的情况下促进凋亡相关基因表达的MTX最佳浓度。其次，我们在转录水平上研究了单独使用MTX（在选定剂量下）或与DEXA（50μg/mL）联合使用对RPE细胞中凋亡、炎症和EMT相关基因表达的影响。
根据RPE细胞中 和 的表达水平，用100μg/mL MTX处理显示出促凋亡作用。MTX（100μg/mL）和DEXA的联合显著降低了炎症相关基因（ ）的表达，表明具有协同抗炎作用。然而，除了部分中和MTX对 和 基因的降低作用外，对与EMT相关的基因（ ）表达没有显著影响。
我们的研究强调了MTX（100μg/mL）对RPE细胞的潜在促凋亡作用以及MTX/DEXA联合治疗的协同抗炎作用。然而，这种联合对与EMT相关的基因没有显著影响。需要进一步研究以阐明这些发现对PVR治疗的临床意义。
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