Calpain-specific breakdown fragment in human drusen.

Autor:	Orihara K; Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Ltd., Portland, OR, USA., Kobayashi-Otsugu M; Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Ltd., Portland, OR, USA., Nakajima E; Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Ltd., Portland, OR, USA.; Department of Oral Rehabilitation and Biosciences, Oregon Health and Science University, Portland, OR, USA., Walkup RD; Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Ltd., Portland, OR, USA.; Department of Oral Rehabilitation and Biosciences, Oregon Health and Science University, Portland, OR, USA., Wilson DJ; Department of Ophthalmology, School of Medicine, Oregon Health and Science University, Portland, OR, USA., Shearer TR; Department of Oral Rehabilitation and Biosciences, Oregon Health and Science University, Portland, OR, USA., Azuma M; Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Ltd., Portland, OR, USA.; Department of Oral Rehabilitation and Biosciences, Oregon Health and Science University, Portland, OR, USA. azumam@ohsu.edu.
Jazyk:	angličtina
Zdroj:	Histology and histopathology [Histol Histopathol] 2024 Feb; Vol. 39 (2), pp. 165-175. Date of Electronic Publication: 2023 Jun 01.
DOI:	10.14670/HH-18-635
Abstrakt:	Purpose: 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 progression. (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)
Databáze:	MEDLINE
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