Co-localisation of advanced glycation end products and D-β-aspartic acid-containing proteins in gelatinous drop-like corneal dystrophy.
OBJECTIVE
Gelatinous drop-like corneal dystrophy (GDLD), also known as familial subepithelial corneal amyloidosis, is an autosomal recessive disorder that causes progressive corneal opacity due to accumulation of amyloid fibrils in the corneal stroma. Genetic analyses have revealed that a mutation in membrane component chromosome 1 surface marker 1 gene is responsible for GDLD. However, the mechanism of amyloid formation in the corneal stroma remains unclear. The present study attempted to reveal the role of advanced glycation end products (AGE) and d-amino acids in amyloid formation in GDLD.


METHODS
Informed consent was obtained from five patients with GDLD, three patients with bullous keratopathy and three patients with interstitial keratitis and all the specimens were analysed. Localisation of amyloid fibrils was analysed using Congo-red and thioflavin T staining. In addition, the localisation of AGE (N(ε)-carboxy(methyl)-L-lysine, pyrraline and pentosidine) and D-β-aspartic acid-containing proteins, a major form of d-amino acid-containing proteins, was analysed immunohistochemically.


RESULTS
In all GDLD specimens, strong immunoreactivity to AGE and D-β-aspartic acid-containing proteins was detected in the subepithelial amyloid-rich region. In contrast, amyloid fibrils, AGE, or D-amino acid-containing proteins were slightly detected in the corneal stroma of patients with bullous keratopathy and interstitial keratitis.


CONCLUSIONS
Abnormally accumulated proteins rich in AGE and D-β-aspartic acid co-localise in the amyloid lesions in GDLD. These results indicate that non-enzymatic post-translational modifications of proteins, including AGE formation and isomerisation of aspartyl residues, will be the cause as well as the result of amyloid fibril formations in GDLD.
Department of Ophthalmology, Tsukuba University Institute of Clinical Medicine, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan. kajiyuichi@gmail.com
Yuichi
Y
Kaji
Tetsuro
T
Oshika
Yutaka
Y
Takazawa
Masashi
M
Fukayama
Noriko
N
Fujii
D000682:Amyloid / Q000378:metabolism; D028226:Amyloidosis, Familial / Q000378:metabolism*; D003317:Corneal Dystrophies, Hereditary / Q000378:metabolism*; D026603:D-Aspartic Acid / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged
D000682:Amyloid; D005136:Eye Proteins; D017127:Glycation End Products, Advanced; D026603:D-Aspartic Acid