Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea.
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.
Araki-Sasaki
K
K
Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
Ando
Y
Y
Nakamura
M
M
Kitagawa
K
K
Ikemizu
S
S
Kawaji
T
T
Yamashita
T
T
Ueda
M
M
Hirano
K
K
Yamada
M
M
Matsumoto
K
K
Kinoshita
S
S
Tanihara
H
H
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
D003224:Congo Red; D007781:Lactoferrin