Topical Administration of Lacritin Is a Novel Therapy for Aqueous-Deficient Dry Eye Disease
Topical Administration of Lacritin Is a Novel Therapy for Aqueous-Deficient Dry Eye Disease
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DOI：
10.1167/iovs.14-13924
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发表时间：
2014-08-01
影响因子：
4.4
通讯作者：
McNamara, Nancy A.
中科院分区：
文献类型：
--
作者：
Vijmasi, Trinka;Chen, Feeling Y. T.;McNamara, Nancy A.
目的。Lacritin是一种泪液糖蛋白，具有促分泌、生殖和有丝分裂的特性。检测干燥综合征(SS)患者泪液中的Lacritin水平，探讨外用Lacritin治疗干性角结膜炎的可能性。方法用C-末端抗体检测14例正常对照组和15例SS患者泪液中Lacritin的含量。在一项配对研究中，自身免疫调节剂(AIRE)基因敲除(KO)小鼠(n=7)在10亩L(左眼)或赋形剂(PBS)对照组(右眼)的基础上，每天治疗3次，连续21天。在基线和治疗后评估泪液分泌和眼表完整性。结果：SS患者每百亩泪液中乳酸蛋白单体(421.8+/-65.3ngSS)和C末端片段蛋白(399.5+/-34.1ngSS)和C-末端片段蛋白(399.5+/-84.3ngvs.399.5+/-84.3ngvs.399.5+/-84.3ngvs.399.5+/-84.3ngP=0.008)明显减少。Aire KO组小鼠泪液分泌量较治疗前增加46%(13.0±-3.5mmvs.8.9+/-2.9mmvs.8.9+/-2.9mmvs.-0.417+/-0.06vs.0.125+/-0.07；P=0.02)。在用催乳素治疗的眼睛中，角膜中K10的表达显著减少，但K12的表达不明显。治疗侧泪腺局部CD4+T细胞浸润较未治疗侧明显减少。结论：SS患者泪液中Lacritin显著减少。局部应用拉西汀具有治疗缺水干眼症的潜力。
PURPOSE. Lacritin is a tear glycoprotein with prosecretory, prosurvival, and mitogenic properties. We examined lacritin levels in the tears of Sjogren's syndrome (SS) patients and explored the therapeutic potential of topical lacritin for the treatment of keratoconjunctivitis sicca.METHODS. Tears from healthy controls (n = 14) and SS patients (n = 15) were assayed for lacritin using a C-terminal antibody. In a paired-eye study, autoimmune regulator (Aire) knockout (KO) mice (n = 7) were treated three times daily for 21 days with 10 mu L of 4 mu M lacritin (left eye) or vehicle (PBS) control (right eye). Tear secretion and ocular surface integrity were assessed at baseline and after treatment. Immunohistochemical staining of CD4+ T cells, cytokeratin-10 (K10), and cytokeratin-12 (K12) expression in the cornea and CD4+ T cell infiltration in the lacrimal glands were assessed.RESULTS. Lacritin monomer (421.8 +/- 65.3 ng [SS] vs. 655.8 +/- 118.9 ng [controls]; P = 0.05) and C-terminal fragment protein (125 +/- 34.1 ng [SS] vs. 399.5 +/- 84.3 ng [controls]; P = 0.008) per 100 mu L of tear eluate were significantly lower in SS patients. In Aire KO mice treated with lacritin, tear secretion increased by 46% (13.0 +/- 3.5 mm vs. 8.9 +/- 2.9 mm; P = 0.01) and lissamine green staining score significantly decreased relative to baseline (-0.417 +/- 0.06 vs. 0.125 +/- 0.07; P = 0.02). Expression of K10 but not K12 in the cornea was significantly decreased in lacritin-treated eyes. Focal CD4+ T cell infiltration of the lacrimal glands was significantly reduced on the lacritin-treated side versus the untreated side.CONCLUSIONS. Lacritin is significantly reduced in the tears of SS patients. Topically administered lacritin has therapeutic potential for the treatment of aqueous-deficient dry eye disease.