On the role of kerato-epithelin in the pathogenesis of 5q31-linked cornealdystrophies

PURPOSE. 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 CDLIILA), granular Groenouw type I (CDGGI), Avellino (CD A), and Reis-Bucklers' (CDRB). All these disorders are characterized by the progressive accumulation of corneal deposits with different structural org anization. Experiments were conducted to determine the role of kerato-epith elin (KE), the product of BIGH3, in the pathogenesis of the diseases. METHODS. KE-15 and KE-2, two rabbit antisera raised against peptides from t he 69-364 and 426-682 amino acid regions of KE respectively, were used for immunohistology of the corneas obtained after keratoplasty in six CDLI pati ents, three CDGGI patients, and one CDA patient. RESULTS. 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 nona myloid inclusions were present, positive staining with both antisera was ob served. CONCLUSIONS. Pathologic amyloid and nonamyloid deposits observed in CDLI, C DGGI-, and CDA-affected corneas are caused by KE accumulation. Different st aining patterns of amyloid and nonamyloid deposits observed with antibodies against the amino and carboxyl termini of KE suggest that two mechanisms o f KE misfolding are implicated in the pathogenesis of 5q31-linked corneal d ystrophies.