title: Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Lactoferrin Glu561Asp is a key polymorphism related to facilitating amyloid formation in corneal amyloidosis with trichiasis.
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Araki-Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ando
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Kitagawa
authors.forename: S
authors.initials: S
authors.lastname: Ikemizu
authors.forename: T
authors.initials: T
authors.lastname: Kawaji
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Kinoshita
authors.forename: H
authors.initials: H
authors.lastname: Tanihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D002648:Child; D003224:Congo Red; D003316:Corneal Diseases / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005140:Eyelashes; D005141:Eyelid Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006201:Hair Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007781:Lactoferrin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
chemical_list: D003224:Congo Red; D007781:Lactoferrin