A Novel Localized Amyloidosis Associated with Lactoferrin in the Cornea

Ando, Yukio; Nakamura, Masaaki; Kai, Hirofumi; Katsuragi, Shoichi; Terazaki, Hisayasu; Nozawa, Takayuki; Okuda, Toshiya; Misumi, Shogo; Matsunaga, Noriko; Hata, Kanako; Tajiri, Takahiro; Shoji, Shuichi; Yamashita, Taro; Haraoka, Katsuki; Obayashi, Konen; Matsumoto, Kousuke; Ando, Masayuki; Uchino, Makoto

doi:10.1097/01.lab.0000017170.26718.89

Cited by 36 publications

(27 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lactoferrin, a major, 78.2-kDa component of tears, has attracted attention because it was found in GDLD amyloid deposits 24 and because lactoferrin fragments can form amyloid fibrils in vitro. 25,26 Although the source of lactoferrin in the amyloid deposits remains to be determined, it may originate from the tear film and penetrate disturbed cell junctions. Alternatively, its presence may be attributable to the overexpression of the lactoferrin gene in epithelial cells although a link between the lactoferrin-and M1S1 gene has been excluded.…”

Section: Discussionmentioning

confidence: 99%

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

Takaoka

Nakamura

Ban

et al. 2007

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

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

Takaoka

Nakamura

Ban

et al. 2007

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…We previously reported that the precursor protein in corneal amyloidosis associated with trichiasis is lactoferrin. 16 Although all of the patients in the previous study were heterozygotes for lactoferrin Glu561Asp gene, no statistical significance was observed when compared with that of the polymorphism in healthy control subjects. Although trichiasis itself is not so uncommon, the incidence of corneal amyloidosis is quite low.…”

mentioning

confidence: 83%

“…Analyses for lactoferrin Glu561Asp were performed via PCR-IMRA as described. 16 When allele for lactoferrin Glu561Asp only exists, the digestion bands (158 bp and 28 bp) are observed.…”

Section: Figurementioning

confidence: 99%

Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea

Araki-Sasaki

2005

British Journal of Ophthalmology

View full text Add to dashboard Cite

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.

show abstract

“…Lf gene analysis in the 3 patients revealed a Glu561Asp mutation, and a compound heterozygote of Ala11Thr and Glu561Asp mutations in 1 patient. Heterozygotic Glu561Asp mutation was found in 44.8% of healthy Japanese volunteers, suggesting that the mutation may not be an essential mutation for amyloid formation (p=0.104), and that Lf was this precursor protein [463].…”

Section: T Gondii Infectionmentioning

confidence: 99%

“…Ando et al [463] reported that in three patients with corneal amyloidosis electrophoresis of amyloid fibrils revealed Lf with and without sugar chains, and N-terminal sequence analysis demonstrated full-length Lf and a truncated tripeptide of N-terminal amino acids, Gly-Arg-Arg. Carboxymethylated wild-type Lf formed amyloid fibrils in vitro.…”

Section: T Gondii Infectionmentioning

confidence: 99%

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

Pr¹,

ota²

2013

J Diabetes Metab

View full text Add to dashboard Cite

Recently, it was suggested that maternal T and potentially B cells transferred during pregnancy and/or the breast milk feeding and their encounter with the antigen in mesenteric lymph nodes might play a role in development of type 1 diabetes mellitus (T1DM). T. gondii infection during gestation and/or after birth may be responsible for development of both T1DM and T2DM in children, adolescents and adults because: a) maternal microchimerism in peripheral blood was demonstrated to be significantly higher in patients with T1DM compared to unaffected siblings and healthy subjects, b) transmission of T. gondii as a Trojan horse in various types of eukaryotic cells, including T and B lymphocytes, c) swallowing by the fetus of amniotic fluid containing infected leukocytes and other cells, d) elimination of T. gondii in the breast milk during lactation, e) involvement of mesenteric lymph nodes after oral infection with the parasite, and f) damage of the myenteric neurons during infection with the parasite in both the animals with streptozotocin-induced diabetes and diabetic patients. Moreover, a significantly lower occurrence of antibodies against T. gondii found in the sera of patients with T1DM compared with their first-degree family members or healthy controls may be due to their T and/or B cell exhaustion perspective caused by chronic infection with the parasite. This suggestion may be supported by the finding that latent toxoplasmosis was associated with markedly reduced lymphocyte B-cell counts responsible for production of antibodies, markedly lower serum IgG, IgM, and IgA levels, and a significant suppression of IL-2. On the other hand, patients with T2DM had increased anti-T. gondii antibodies significantly more frequently than respective controls. Impaired vascular endothelial function characteristic for the patients with diabetes mellitus may be at least in part due to the preferential T. gondii infection of endothelial cells. Vitamin D and minocycline exerted beneficial effects on development and clinical course of diabetes mellitus probably because of their immunomodulatory and antitoxoplasmatic activities. These data strongly suggest that the parasite play an important role in development of both types of diabetes mellitus.

show abstract

A Novel Localized Amyloidosis Associated with Lactoferrin in the Cornea

Cited by 36 publications

References 41 publications

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

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

Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

Contact Info

Product

Resources

About