Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea
Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea
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DOI：
10.1136/bjo.2004.056804
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发表时间：
2005-06-01
影响因子：
4.1
通讯作者：
Tanihara, H
中科院分区：
文献类型：
--
作者：
Araki-Sasaki, K;Ando, Y;Tanihara, H
目的：探讨继发性角膜淀粉样变性合并倒睫的发病机制。方法：对9例患者进行眼科检查，以确定继发性角膜淀粉样变性合并倒立。角膜活检标本采用刚果红染色和抗人乳铁蛋白抗体免疫组织化学方法。采用单链构象多态(SSCP)、直接DNA序列分析和聚合酶链式反应(PCR)诱导的突变限制性内切酶分析(IMRA)检测乳铁蛋白基因的多态性。结果：所有患者均有倒睫至少1年，1眼倒立均有淀粉样物沉积。眼科检查发现8例为凝胶型淀粉样物沉积，1例为晶格型淀粉样物沉积。刚果红染色的活组织角膜样本研究显示，角膜上皮细胞正下方呈阳性染色。刚果红染色阳性的所有组织均可检测到抗人乳铁蛋白抗体的免疫反应性。乳铁蛋白基因分析显示，7例患者为Glu561Asp杂合子，2例为纯合子。结论：乳铁蛋白Glu561Asp基因是促进角膜淀粉样变性合并倒睫中淀粉样蛋白形成的关键基因。
Aim: To elucidate the pathogenic mechanism of amyloid formation in corneal amyloidosis with trichiasis.Methods: Ophthalmological examination was performed in nine patients to determine secondary corneal amyloidosis with trichiasis. Congo red staining and immunohistochemistry using anti- human lactoferrin antibody were used for biopsied corneal samples. For genetic analyses, single strand conformation polymorphism ( SSCP), direct DNA sequence analysis, and polymerase chain reaction ( PCR) induced mutation restriction analysis ( IMRA) were employed to detect lactoferrin gene polymorphism.Results: All patients had had trichiasis at least for 1 year, and all amyloid- like deposits were found in one eye with trichiasis. Ophthalmological examination revealed that eight patients showed gelatinous type of amyloid deposition and one showed lattice type of amyloid deposition. Studies of biopsied corneal samples with Congo red stain revealed positive staining just under the corneal epithelial cells. Immunoreactivity of anti- human lactoferrin antibodies was recognised in all tissues with positive Congo red staining. Lactoferrin gene analysis revealed that seven patients were heterozygotic and two were homozygotic for lactoferrin Glu561Asp. The frequency of the polymorphism in the patients was significantly different from that in 56 healthy control subjects.Conclusion: Lactoferrin Glu561Asp is a key polymorphism related to facilitating amyloid formation in corneal amyloidosis with trichiasis.