Ultrasound (US) assisted drug delivery is receiving interest in treating posterior eye diseases, such as diabetic retinopathy due to its ability to maximize drug penetration into difficult to reach tissues. Despite its promise, the technique has only been investigated using healthy cell and tissue models, with no evidence to date about its safety in active disease. As a result, the aim of this study was to evaluate the safety of US administration in vitro in retinal pigment epithelial cells under normal and high glucose conditions. US protocols within the presently accepted safety threshold were applied and their influence on cell membrane and tight junction integrity as well as intracellular inflammation was evaluated using lactate dehydrogenase (LDH), zona occludens‐1 (ZO‐1), fluorescein isothiocyanate (FITC)‐dextran dye leak and nuclear factor‐kappaB (NF‐κB) assays, respectively. Under high glucose conditions, US application increased LDH release and resulted in loss of ZO‐1 labeling at 2 h; however, normal levels were restored within 24 h. US within its safety parameters did not induce any FITC‐dextran dye leak or NF‐κB nuclear translocation in normal or high glucose conditions. In conclusion, our results suggest that while high glucose conditions increase cell susceptibility to US‐mediated stress, basal conditions can be restored within 24 h without long‐lasting cell damage.

中文翻译：

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高血糖对视网膜色素上皮细胞超声安全性的影响

超声 (US) 辅助药物递送在治疗后眼部疾病（例如糖尿病性视网膜病变）方面受到关注，因为它能够最大限度地将药物渗透到难以到达的组织中。尽管有前景，但该技术仅使用健康细胞和组织模型进行了研究，迄今为止尚无证据表明其在活动性疾病中的安全性。因此，本研究的目的是评估 US 在正常和高糖条件下体外给药视​​网膜色素上皮细胞的安全性。应用目前接受的安全阈值内的美国方案，并使用乳酸脱氢酶 (LDH)、封闭带-1 (ZO-1) 评估它们对细胞膜和紧密连接完整性以及细胞内炎症的影响。荧光素异硫氰酸酯 (FITC)-葡聚糖染料泄漏和核因子-κB (NF-κB) 测定，分别。在高糖条件下，US 应用增加了 LDH 释放并导致 ZO-1 标记在 2 小时时丢失；然而，正常水平在 24 小时内恢复。在其安全参数范围内，US 在正常或高葡萄糖条件下未引起任何 FITC-葡聚糖染料泄漏或 NF-κB 核易位。总之，我们的结果表明，虽然高糖条件会增加细胞对 US 介导的压力的敏感性，但基础条件可以在 24 小时内恢复，而不会造成持久的细胞损伤。在其安全参数范围内，US 在正常或高葡萄糖条件下未引起任何 FITC-葡聚糖染料泄漏或 NF-κB 核易位。总之，我们的结果表明，虽然高糖条件会增加细胞对 US 介导的压力的敏感性，但基础条件可以在 24 小时内恢复，而不会造成持久的细胞损伤。在其安全参数范围内，US 在正常或高葡萄糖条件下未引起任何 FITC-葡聚糖染料泄漏或 NF-κB 核易位。总之，我们的结果表明，虽然高糖条件会增加细胞对 US 介导的压力的敏感性，但基础条件可以在 24 小时内恢复，而不会造成持久的细胞损伤。