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Inhibition of matrix metalloproteinase 9 enhances rod survival in the s334ter-Line3 retinitis pigmentosa model

Title
Inhibition of matrix metalloproteinase 9 enhances rod survival in the s334ter-Line3 retinitis pigmentosa model
Authors
Shin J.-A.Kim H.S.Vargas A.Yu W.-Q.Eom Y.S.Craft C.M.Lee E.-J.
Ewha Authors
신정아
SCOPUS Author ID
신정아scopus
Issue Date
2016
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 11, no. 11
Publisher
Public Library of Science
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Retinitis Pigmentosa (RP) is one of the most common forms of inherited visual loss with the initial degeneration of rod photoreceptors, followed by a progressive cone photoreceptor deterioration. Coinciding with this visual loss, the extracellular matrix (ECM) is reorganized, which alters matrix metalloproteinase (MMP) activity levels. A potential pathological role of MMPs, MMP-9 in particular, involves an excitotoxicity-mediated physiological response. In the current study, we examine the MMP-9 and MMP-2 expression levels in the rhodopsin S334ter-line3 RP rat model and investigate the impact of treatment with SB-3CT, a specific MMP-9 and MMP-2 inhibitor, on rod cell survival was tested. Retinal MMP-9 and MMP-2 expression levels were quantified by immunoblot analysis from S334ter-line3 rats compared to controls. Gelatinolytic activities of MMP-9 and MMP-2 by zymography were examined. The geometry of rod death was further evaluated using Voronoi analysis. Our results revealed that MMP-9 was elevated while MMP-2 was relatively unchanged when S334terline 3 retinas were compared to controls. With SB-3CT treatment, we observed gelatinolytic activity of both MMPs was decreased and diminished clustering associated with rod death, in addition to a robust preservation of rod photoreceptors. These results demonstrate that up-regulation of MMP-9 in retinas of S334ter-line3 are associated with rod death. The application of SB-3CT dramatically interferes with mechanisms leading to apoptosis in an MMP-9-dependent manner. Future studies will determine the feasibility of using SB-3CT as a potential therapeutic strategy to slow progression of vision loss in genetic inherited forms of human RP.Copyright: © 2016 Shin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI
10.1371/journal.pone.0167102
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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