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玻璃体内滴注纤溶酶原可消除 B6.129P2-Plg(tm1Jld) 转基因小鼠(一种眼型黏多糖贮积症的模型)的眼部病变。

Conjunctival instillation of plasminogen eliminates ocular lesion in B6.129P2-Plg(tm1Jld) transgenic mice, a model of ligneous conjunctivitis.

机构信息

Division Pharmacology, Department of Neuroscience, School of Medicine, "Federico II" University of Naples, Via Pansini, 5, 80131 Naples, Italy.

出版信息

Pharmacol Res. 2013 Aug;74:45-8. doi: 10.1016/j.phrs.2013.04.012. Epub 2013 May 16.

Abstract

Ligneous conjunctivitis is a severe and rare chronic "idiopathic membraneous" conjunctivitis, characterized by the formation of pseudomembranes mostly on the palpebral surfaces that progressively replace the normal mucosa. Evidence has been provided that ligneous conjunctivitis is caused by a severe systemic plasminogen deficiency with decreased plasminogen antigen and decreased plasminogen functional activities. Objective of the present study is to verify the hypothesis that a topical eye application of plasminogen is able to ameliorate the consequences of this disease. Here we report the results of pre-clinical studies performed to investigate the therapeutic effectiveness of an eye-drop plasminogen preparation in B6.129P2-Plg(tm1Jld) transgenic mice, a model of ligneous conjunctivitis. The entity of protection mediated by plasminogen was evaluated by measuring the extent of the eye lesion by means of a computerized system and dedicated software. The results of the present study clearly showed that the administration for six times a day of plasminogen eye-drop solution in the lesioned eye of animals knock-out for plasminogen gene and developing ligneous conjunctivitis caused a dose and time related reduction of the extent of the ocular lesion. These findings may pave the road for the pharmacological treatment of the ocular lesion associated to the ligneous conjunctivitis that at the present is surgically treated by removing the pseudomembranes generated on the eye.

摘要

细菌性结膜炎是一种严重且罕见的慢性“特发性膜性”结膜炎,其特征是在眼睑表面形成假膜,逐渐取代正常的黏膜。有证据表明,细菌性结膜炎是由严重的全身纤维蛋白溶酶原缺乏引起的,表现为纤维蛋白溶酶原抗原减少和纤维蛋白溶酶原功能活性降低。本研究的目的是验证局部眼部应用纤维蛋白溶酶原能够改善这种疾病的后果这一假说。我们在此报告了在 B6.129P2-Plg(tm1Jld)转基因小鼠(细菌性结膜炎模型)中进行的临床前研究的结果,以研究滴眼用纤维蛋白溶酶原制剂的治疗效果。通过使用计算机系统和专用软件来测量眼部病变的程度,评估纤维蛋白溶酶原介导的保护程度。本研究的结果清楚地表明,在基因敲除的动物眼部病变中每天六次局部应用纤维蛋白溶酶原滴眼溶液,可引起与剂量和时间相关的眼部病变程度减少。这些发现可能为治疗与细菌性结膜炎相关的眼部病变铺平道路,目前该病通过手术切除眼部产生的假膜来治疗。

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