Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea

Abstract

Aim: 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. Conclusion: Lactoferrin Glu561Asp is a key polymorphism related to facilitating amyloid formation in corneal amyloidosis with trichiasis.

Phenotypic Investigation of Cell Junction–Related Proteins in Gelatinous Drop-Like Corneal Dystrophy

“…This finding raises the possibility that the lactoferrin we observed in the amyloid deposits originated not only from tear fluid, but also from corneal epithelial cells. Araki-Sasaki et al 29 showed a significantly increased frequency of the lactoferrin polymorphism Glu561Asp in patients with secondary corneal amyloidosis. We did not address this question in the current investigation, and studies are under way to determine whether lactoferrin polymorphism is a key factor in the formation of amyloid deposits in GDLD.…”

Chromosomal sharing in atypical cases of gelatinous drop-like corneal dystrophy

“…On the other hand, the amyloid in GDLD has been found to react immunohistochemically with human lactoferrin antibodies and lactoferrin may play a role in amyloid depositions in the cornea. 17,18 The importance of lactoferrin might indicate that several steps may be responsible for amyloid depositions in GDLD, and the malfunctions of TACSTD2 alone are not enough to account for severe corneal amyloidoses in GDLD. The complex mechanism of amyloid deposition might be one cause of the phenotypic variability presented here.…”

A Novel Single-Nucleotide Polymorphism in the Lactoferrin Gene Is Associated with Susceptibility to Diarrhea in North American Travelers to Mexico

“…We choose to study SNPs in the lactoferrin gene, because this is an important element of the intestinal innate immune system, and SNPs in various regions of this gene are associated with cancer [29], periodontitis [30], and corneal amyloidosis [31].…”