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一种新型联合治疗 Tβ4/VIP 可预防高血糖诱导的人角膜上皮细胞变化。

A Novel Combination Therapy Tβ4/VIP Protects against Hyperglycemia-Induced Changes in Human Corneal Epithelial Cells.

机构信息

Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Department of Health Sciences, University of Central Florida College of Health Professions and Sciences, Orlando, FL 32816, USA.

出版信息

Biosensors (Basel). 2023 Nov 7;13(11):974. doi: 10.3390/bios13110974.

DOI:10.3390/bios13110974
PMID:37998149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10669755/
Abstract

Despite the prevalence of diabetic retinopathy, the majority of adult diabetic patients develop visually debilitating corneal complications, including impaired wound healing. Unfortunately, there is limited treatment for diabetes-induced corneal damage. The current project investigates a novel, peptide-based combination therapy, thymosin beta-4 and vasoactive intestinal peptide (Tβ4/VIP), against high-glucose-induced damage to the corneal epithelium. Electric cell-substrate impedance sensing (ECIS) was used for real-time monitoring of barrier function and wound healing of human corneal epithelial cells maintained in either normal glucose (5 mM) or high glucose (25 mM) ± Tβ4 (0.1%) and VIP (5 nM). Barrier integrity was assessed by resistance, impedance, and capacitance measurements. For the wound healing assay, cell migration was also monitored. Corneal epithelial tight junction proteins (ZO-1, ZO-2, occludin, and claudin-1) were assessed to confirm our findings. Barrier integrity and wound healing were significantly impaired under high-glucose conditions. However, barrier function and cell migration significantly improved with Tβ4/VIP treatment. These findings were supported by high-glucose-induced downregulation of tight junction proteins that were effectively maintained similar to normal levels when treated with Tβ4/VIP. These results strongly support the premise that Tβ4 and VIP work synergistically to protect corneal epithelial cells against hyperglycemia-induced damage. In addition, this work highlights the potential for significant translational impact regarding the treatment of diabetic patients and associated complications of the cornea.

摘要

尽管糖尿病视网膜病变较为普遍，但大多数成年糖尿病患者会出现视觉受损的角膜并发症，包括伤口愈合受损。不幸的是，针对糖尿病引起的角膜损伤，目前的治疗方法十分有限。本项目研究了一种新型的、基于肽的联合治疗方法，即胸腺肽 β4 和血管活性肠肽（Tβ4/VIP），用于对抗高葡萄糖诱导的角膜上皮损伤。采用电动细胞-底物阻抗传感（ECIS）技术实时监测人角膜上皮细胞在正常葡萄糖（5mM）或高葡萄糖（25mM）+Tβ4（0.1%）和 VIP（5nM）中的屏障功能和伤口愈合情况。通过电阻、阻抗和电容测量评估屏障完整性。对于伤口愈合测定，还监测了细胞迁移。评估角膜上皮紧密连接蛋白（ZO-1、ZO-2、occludin 和 claudin-1）以证实我们的发现。在高葡萄糖条件下，屏障完整性和伤口愈合明显受损。然而，Tβ4/VIP 治疗可显著改善屏障功能和细胞迁移。这些发现得到了高葡萄糖诱导的紧密连接蛋白下调的支持，当用 Tβ4/VIP 处理时，这些紧密连接蛋白的水平被有效维持在接近正常水平。这些结果有力地支持了 Tβ4 和 VIP 协同作用保护角膜上皮细胞免受高血糖损伤的前提。此外，这项工作突出了针对糖尿病患者和相关角膜并发症的治疗具有重要的转化潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e0/10669755/ce23261ed9cf/biosensors-13-00974-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e0/10669755/e9d88e56bfd3/biosensors-13-00974-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e0/10669755/ce23261ed9cf/biosensors-13-00974-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e0/10669755/63582b1a9070/biosensors-13-00974-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e0/10669755/b27897bde039/biosensors-13-00974-g003.jpg
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