INS365 suppresses, epithelial integrity loss of corneal by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model
INS365 suppresses, epithelial integrity loss of corneal by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model
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DOI：
10.1089/10807680260218524
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发表时间：
2002-08-01
影响因子：
2.3
通讯作者：
Nakata, K
中科院分区：
文献类型：
--
作者：
Fujihara, T;Murakami, T;Nakata, K
P2Y(2)受体激动剂，如UTP和ATP，在体外刺激杯状细胞分泌粘蛋白。因此，黏液蛋白兴奋剂可能是治疗干眼综合征的良好候选者，因为黏液蛋白增加了泪膜的稳定性，并防止眼表干燥。INS365是一种比UTP更稳定的P2Y(2)受体激动剂。在本研究中，我们观察了其在正常兔眼中释放杯状细胞粘蛋白和保护干燥引起的角膜损伤的作用。在结膜囊内注入INS365溶液或生理盐水后，进行粘蛋白分泌印迹细胞学检查。用周期酸和希夫（PAS）试剂对标本进行染色，并用计算机软件计算染色面积。INS365剂量依赖性地减少结膜杯状细胞的PAS染色面积从2至15分钟后施用。此外，我们还利用兔短期干眼模型来评估INS365滴眼液是否可以防止有镜阻塞的眨眼所产生的任何损伤。INS365在浓度大于0.1% w/v时显著抑制角膜损伤。这些结果表明，这种P2Y(2)激动剂是治疗干眼病的良好候选者。
P2Y(2) receptor agonists, like UTP and ATP, stimulate mucin secretion from goblet cells in vitro. Therefore, mucin stimulants could be good candidates for the treatment of dry eye syndrome because mucin increases the tear film stability and protects against desiccation of ocular surface. INS365 is a more stable P2Y(2) receptor agonist than UTP. In the present study, we evaluated, in normal rabbit eyes, its effectiveness to release mucin from goblet cells and to protect the corneal damage induced by desiccation. For mucin secretion, impression cytology was performed following the instillation of INS365 solution or saline into the conjunctival sac. The specimens were stained with periodic acid and Schiff (PAS) reagent, and then the staining area was calculated using computer software. INS365 dose-dependently decreased the PAS staining area of conjunctival goblet cells from 2 to 15 min post-application. Furthermore, we utilized the rabbit short-term dry eye model to evaluate if INS365 eyedrops could protect against any of the damage produced by blockage of blinking with ocular speculum. INS365 significantly suppressed corneal damage at concentrations of more than 0.1% w/v. These results suggest that this P2Y(2) agonist is a good candidate for the treatment of dry eye disease.