FAMILIAL SUBEPITHELIAL CORNEAL AMYLOIDOSIS - A LACTOFERRIN-RELATED AMYLOIDOSIS

Purpose. To isolate the protein that collects in increased amounts ben eath the corneal epithelium in familial subepithelial corneal amyloido sis (FSCA), also known as gelatinous droplike corneal dystrophy, and t o identify it by N-terminal amino acid sequencing. Methods. Peptides r esulting from pepsin digestion of a unique protein isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from frozen tissue from two corneas with FSCA were purified by high-pressure liquid chrom atography followed by protein sequence analysis. The protein was ident ified by amino acid sequencing, Western blotting, and immunohistochemi stry. Results. A protein was identified in two corneas with FSCA that was not present in normal corneas or in corneas with other disorders. The amino acid sequences of two peptides derived from this protein wer e identical to portions of lactoferrin. The unique protein reacted wit h rabbit antihuman lactoferrin after Western blotting. The presence of lactoferrin in the amyloid within affected corneas was confirmed usin g the immunoperoxidase method on formalin-fixed, paraffin-embedded tis sue sections and lactoferrin antiserum. Conclusions. Corneal tissue wi th FSCA contains lactoferrin, and this is the first form of amyloidosi s found to be associated with this protein. Because lactoferrin is a p roduct of lacrimal glands, the corneal lactoferrin may be derived from the tears. Because the gene for lactoferrin is on chromosome 3 (3q21- q23), this locus is a potential site for the FSCA gene.