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Calpain-specific breakdown fragment in human drusen

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dc.contributor.authorOrihara, Kana
dc.contributor.authorKobayashi Otsugu, Momoko
dc.contributor.authorNakajima, Emi
dc.contributor.authorWalkup, Ryan D.
dc.contributor.authorWilson, David J.
dc.contributor.authorShearer, Thomas R.
dc.contributor.authorAzuma, Mitsuyoshi
dc.date.accessioned2024-01-29T09:15:08Z
dc.date.available2024-01-29T09:15:08Z
dc.date.issued2024
dc.description.abstractPurpose. With aging and age-related macular dystrophy (AMD), proteolytic fragments are deposited in extracellular drusen located between the RPE and Bruch’s membrane. Localized hypoxia may be a risk factor for AMD. Our hypothesis is that following hypoxia, activation of proteolytic enzymes called calpains may cause proteolysis/degeneration of retinal cells and RPE. No direct evidence has yet demonstrated activation of calpains in AMD. The purpose of the present study was to identify calpain-cleaved proteins in drusen. Methods. Seventy-six (76) drusen were analyzed in human eye sections from six normal and twelve AMD human donor eyes. The sections were subjected to immunofluorescence for the calpain-specific 150 kDa breakdown product from α-spectrin, SBDP150-a marker for calpain activation, and for recoverin-a marker for photoreceptor cells. Results. Among 29 nodular drusen, 80% from normal eyes and 90% from AMD eyes stained positive for SBDP150. Among 47 soft drusen, mostly from AMD eyes, 72% stained positive for SBDP150. Thus, the majority of both soft and nodular drusen from AMD donors contained SBDP150. Conclusions. SBDP150 was detected for the first time in soft and nodular drusen from human donors. Our results suggest that calpain-induced proteolysis participates in the degeneration of photoreceptors and/or RPE cells during aging and AMD. Calpain inhibitors may ameliorate AMD progressiones
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dc.format.extent11es
dc.identifier.citationHistology and Histopathology Vol. 39, nº2 (2024)
dc.identifier.doihttps://doi.org/10.14670/HH-18-635
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/137907
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCalpaines
dc.subjectα-spectrines
dc.subjectSBDP150es
dc.subjectAMD agerelated macular degenerationes
dc.subjectDrusenes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleCalpain-specific breakdown fragment in human drusenes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.39, nº2 (2024)