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干扰素 α-2b 处理的视网膜色素上皮细胞中细胞凋亡、炎症、血管生成和神经营养因子表达的评估。

Evaluation of Apoptosis, Inflammation, Angiogenesis, and Neuroprotection Gene Expression in Retinal Pigmented Epithelial Cell Treated with Interferon α-2b.

机构信息

Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

J Interferon Cytokine Res. 2023 Jul;43(7):299-306. doi: 10.1089/jir.2023.0028. Epub 2023 Jun 8.

DOI:10.1089/jir.2023.0028
PMID:37289822
Abstract

Angiogenesis, retinal neuropathy, and inflammation are the main molecular features of diabetic retinopathy (DR) and should be taken into consideration for potential treatment approaches. Retinal pigmented epithelial (RPE) cells play a major role in DR progression. This study evaluated the effect of interferon (IFN) α-2b on the expression of genes involved in apoptosis, inflammation, neuroprotection, and angiogenesis in RPE cells. RPE cells were cocultured with IFN α-2b at 2 doses (500 and 1,000 IU) and treatment periods (24 and 48 h). The quantitative relative expression of genes (, , , , and ) was evaluated in the treated versus control cells through real-time polymerase chain reaction (PCR). The result of this study demonstrated that IFN treatment at 1,000 IU (48 h) led to significant upregulation of , , , and ; however, the ratio was not statistically altered from 1:1, in any of the treatment patterns. We also showed that expression was downregulated in RPE cells treated with 500 IU for 24 h. It can be concluded that IFN α-2b was safe ( ∼1:1) and enhanced neuroprotection at 1,000 IU (48 h); however-at the same time-IFN α-2b induced inflammation in RPE cells. Moreover, the antiangiogenic effect of IFN α-2b was solely observed in RPE cells treated with 500 IU (24 h). It seems that IFN α-2b in lower doses and short duration exerts antiangiogenic effects and in higher doses and longer duration has neuroprotective and inflammatory effects. Hence, appropriate concentration and duration of treatment, according to the type and stage of the disease, should be considered to achieve success in IFN therapy.

摘要

血管生成、视网膜神经病变和炎症是糖尿病视网膜病变(DR)的主要分子特征,应考虑将其作为潜在的治疗方法。视网膜色素上皮(RPE)细胞在 DR 进展中起主要作用。本研究评估了干扰素(IFN)α-2b 对 RPE 细胞中凋亡、炎症、神经保护和血管生成相关基因表达的影响。RPE 细胞与 IFNα-2b 在 2 个剂量(500 和 1000IU)和治疗时间(24 和 48h)下共培养。通过实时聚合酶链反应(PCR)在处理过的细胞与对照细胞中评估基因(、、、和)的定量相对表达。研究结果表明,IFN 治疗剂量为 1000IU(48h)导致、、和显著上调;然而,在任何治疗模式下,比值均未从 1:1 统计学改变。我们还表明,在 500IU 处理 24h 的 RPE 细胞中,表达下调。可以得出结论,IFNα-2b 在 1000IU(48h)时是安全的(~1:1)并增强了神经保护作用;然而,同时,IFNα-2b 在 RPE 细胞中诱导了炎症。此外,IFNα-2b 的抗血管生成作用仅在 500IU(24h)处理的 RPE 细胞中观察到。似乎 IFNα-2b 在较低剂量和较短时间内发挥抗血管生成作用,在较高剂量和较长时间内具有神经保护和炎症作用。因此,应根据疾病的类型和阶段考虑适当的治疗浓度和持续时间,以实现 IFN 治疗的成功。

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