Immunohistology of kerato-epithelin in corneal stromal dystrophies associated with R124 mutations of the BIGH3 gene

Purpose. To investigate corneal deposits associated with kerato-epithelin (KE) in three corneal dystrophies harboring mutations at Arg-124 in the BIGH3 gene. Methods. Six patients with Avellino corneal dystrophy (ACD) associated with R124H, one patient with superficial granular corneal dystrophy (SGCD) associated with R124L, and seven patients with lattice corneal dystrophy type 1 (CDL1) associated with R124C were examined. Corneal buttons obtained during keratoplasties were stained with Masson's trichrome and with Congo red, and immunostained with antibodies specific for N-terminal and C-terminal portions of KE (KE-15 and KE-2, respectively). Results. In all corneas with ACD, subepithelial to midstromal deposits of granular material stained with KE-2 and KE-15. However, deep stromal deposits containing amyloid reacted with KE-2, but not KE-15. Granular deposits in the subepithelial layer observed in SGCD stained intensely with KE-2 and KE-15. In all corneas with CDL1, subepithelial and midstromal amyloid deposits stained with KE-2; these deposits did not stain with KE-15. Deposits between the epithelial layer and Bowman's layer stained with Masson's trichrome but not with Congo red in five of the seven corneas; these deposits were stained with both KE-2 and KE-15. Conclusions. Deposits in corneal buttons involved by ACD, SGCD, and CDL1 included forms of the BIGH3 gene product, KE. An N-terminal sequence of KE may be related to formation of amyloid associated with R124 mutations.