Department of Ophthalmology, Inje University College of Medicine, Inje University Busan Paik Hospital, Busan, 47392, Korea.
Department of Biochemistry and Molecular Biology, The George Washington University School of Medicine, Washington D.C, USA.
Sci Rep. 2018 Jul 12;8(1):10500. doi: 10.1038/s41598-018-28861-5.
This study evaluated the clinical activity of RGN-259 (thymosin β4) in comparison with cyclosporine A (CsA), diquafosol (DQS), and lifitegrast (LFA) in a murine model of dry eye. The model was NOD.B10-H2 mice in a 30-40% humidified environment together with daily scopolamine hydrobromide injections for 10 days. After desiccation stress, all drugs were evaluated after 10 treatment days. RGN-259 increased tear production similar to that in the DQS- and LFA-treated mice while CsA was inactive. RGN-259 improved corneal smoothness and decreased fluorescein staining similar to that of LFA group while CsA and DQS were inactive. Corneal epithelial detachment was reduced by RGN-259, and DQS and LFA showed similar activity but the CsA was inactive. RGN-259 increased conjunctival goblet cells and mucin production comparable to that seen with CsA, while DQS and LFA were inactive. RGN-259 reduced the over-expression of inflammatory factors comparable to that with CsA and LFA, while DQS was inactive. RGN-259 increased mucin production comparable to that observed with CsA, while DQS and LFA were inactive. In conclusion, RGN-259 promoted recovery of mucins and goblet cells, improved corneal integrity, and reduced inflammation in a dry eye mouse model and was equal to or more effective than prescription treatments.
本研究评估了 RGN-259（胸腺肽 β4）在干眼症小鼠模型中与环孢素 A（CsA）、地夸磷索（DQS）和利福平（LFA）相比的临床疗效。该模型为 NOD.B10-H2 小鼠，在 30-40%湿度环境下，每天接受氢溴酸东莨菪碱注射 10 天。干燥应激后，所有药物在 10 天治疗后进行评估。RGN-259 增加泪液分泌的作用与 DQS 和 LFA 治疗的小鼠相似，而 CsA 则无作用。RGN-259 改善角膜平整度和减少荧光素染色的作用与 LFA 组相似，而 CsA 和 DQS 则无作用。RGN-259 减少了角膜上皮脱落，DQS 和 LFA 表现出相似的活性，但 CsA 无作用。RGN-259 增加结膜杯状细胞和粘蛋白产生的作用与 CsA 相似，而 DQS 和 LFA 则无作用。RGN-259 减少了炎症因子的过度表达，与 CsA 和 LFA 相似，而 DQS 则无作用。RGN-259 增加粘蛋白产生的作用与 CsA 相似，而 DQS 和 LFA 则无作用。总之，RGN-259 促进了粘蛋白和杯状细胞的恢复，改善了角膜完整性，减少了干眼症小鼠模型中的炎症，与处方治疗等效或更有效。
