title: Benzalkonium chloride accelerates the formation of the amyloid fibrils of corneal dystrophy-associated peptides.
abstract: Corneal dystrophies are genetic disorders resulting in progressive corneal clouding due to the deposition of amyloid fibrils derived from keratoepithelin, also called transforming growth factor β-induced protein (TGFBI). The formation of amyloid fibrils is often accelerated by surfactants such as sodium dodecyl sulfate (SDS). Most eye drops contain benzalkonium chloride (BAC), a cationic surfactant, as a preservative substance. In the present study, we aimed to reveal the role of BAC in the amyloid fibrillation of keratoepithelin-derived peptides in vitro. We used three types of 22-residue synthetic peptides covering Leu110-Glu131 of the keratoepithelin sequence: an R-type peptide with wild-type R124, a C-type peptide with C124 associated with lattice corneal dystrophy type I, and a H-type peptide with H124 associated with granular corneal dystrophy type II. The time courses of spontaneous amyloid fibrillation and seed-dependent fibril elongation were monitored in the presence of various concentrations of BAC or SDS using thioflavin T fluorescence. BAC and SDS accelerated the fibrillation of all synthetic peptides in the absence and presence of seeds. Optimal acceleration occurred near the CMC, which suggests that the unstable and dynamic interactions of keratoepithelin peptides with amphipathic surfactants led to the formation of fibrils. These results suggest that eye drops containing BAC may deteriorate corneal dystrophies and that those without BAC are preferred especially for patients with corneal dystrophies.
authors.affiliation: From the Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan and.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kato
authors.affiliation: From the Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan and.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yagi
authors.affiliation: the Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kaji
authors.affiliation: the Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Oshika
authors.affiliation: From the Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan and. Electronic address: ygoto@protein.osaka-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000682:Amyloid / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001548:Benzalkonium Compounds / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D003316:Corneal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D003902:Detergents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000099222:betaIG-H3 Protein
chemical_list: D000682:Amyloid; D001548:Benzalkonium Compounds; D003902:Detergents; D016326:Extracellular Matrix Proteins; D009883:Ophthalmic Solutions; D010455:Peptides; D012967:Sodium Dodecyl Sulfate; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
keywords: Amyloid; Cornea; Fluorescence; Microscopy; Pathogenesis; Peptides; Protein Aggregation