Korvatska E, Munier F L, Chaubert P, Wang M X, Mashima Y, Yamada M, Uffer S, Zografos L, Schorderet D F
Unit of Molecular Genetics, University of Lausanne, Switzerland.
Invest Ophthalmol Vis Sci. 1999 Sep;40(10):2213-9.
Recently, the authors identified a gene, BIGH3, in which different mutations cause a group of hereditary corneal dystrophies: lattice type I and IIIA (CDLI and CDLIIIA), granular Groenouw type I (CDGGI), Avellino (CDA), and Reis-Bücklers' (CDRB). All these disorders are characterized by the progressive accumulation of corneal deposits with different structural organization. Experiments were conducted to determine the role of kerato-epithelin (KE), the product of BIGH3, in the pathogenesis of the diseases.
KE-15 and KE-2, two rabbit antisera raised against peptides from the 69-364 and 426 - 682 amino acid regions of KE respectively, were used for immunohistology of the corneas obtained after keratoplasty in six CDLI patients, three CDGGI patients, and one CDA patient.
The nonamyloid deposits observed in CDGGI stained intensively with KE-15 and KE-2, whereas the amyloid deposits in all analyzed CDLI corneas reacted to KE-2 but not to KE-15. In the CDA cornea, where amyloid and nonamyloid inclusions were present, positive staining with both antisera was observed.
Pathologic amyloid and nonamyloid deposits observed in CDLI, CDGGI-, and CDA-affected corneas are caused by KE accumulation. Different staining patterns of amyloid and nonamyloid deposits observed with antibodies against the amino and carboxyl termini of KE suggest that two mechanisms of KE misfolding are implicated in the pathogenesis of 5q31-linked corneal dystrophies.
最近，作者鉴定出一个基因BIGH3，该基因的不同突变会导致一组遗传性角膜营养不良症，即I型和IIIA型格子状角膜营养不良（CDLI和CDLIIIA）、颗粒状Groenouw I型角膜营养不良（CDGGI）、阿韦利诺角膜营养不良（CDA）和Reis-Bücklers角膜营养不良（CDRB）。所有这些疾病的特征都是角膜沉积物逐渐积累，且结构组织不同。进行实验以确定BIGH3基因产物角膜上皮素（KE）在这些疾病发病机制中的作用。
使用KE-15和KE-2这两种兔抗血清，它们分别是针对KE的69 - 364和426 - 682氨基酸区域的肽段产生的，用于对6例CDLI患者、3例CDGGI患者和1例CDA患者角膜移植术后获得的角膜进行免疫组织学研究。
在CDGGI中观察到的非淀粉样沉积物被KE-15和KE-2强烈染色，而在所有分析的CDLI角膜中的淀粉样沉积物与KE-2反应，但与KE-15不反应。在同时存在淀粉样和非淀粉样包涵体的CDA角膜中，观察到两种抗血清均呈阳性染色。
在受CDLI、CDGGI和CDA影响的角膜中观察到的病理性淀粉样和非淀粉样沉积物是由KE积累引起的。用针对KE氨基末端和羧基末端的抗体观察到的淀粉样和非淀粉样沉积物的不同染色模式表明，KE错误折叠的两种机制与5q31连锁角膜营养不良的发病机制有关。
