Cargando…

NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration

Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associate...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Yujuan, Hanus, Jakub W., Abu-Asab, Mones S., Shen, Defen, Ogilvy, Alexander, Ou, Jingxing, Chu, Xi K., Shi, Guangpu, Li, Wei, Wang, Shusheng, Chan, Chi-Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730317/
https://www.ncbi.nlm.nih.gov/pubmed/26760997
http://dx.doi.org/10.3390/ijms17010073
_version_ 1782412374836248576
author Wang, Yujuan
Hanus, Jakub W.
Abu-Asab, Mones S.
Shen, Defen
Ogilvy, Alexander
Ou, Jingxing
Chu, Xi K.
Shi, Guangpu
Li, Wei
Wang, Shusheng
Chan, Chi-Chao
author_facet Wang, Yujuan
Hanus, Jakub W.
Abu-Asab, Mones S.
Shen, Defen
Ogilvy, Alexander
Ou, Jingxing
Chu, Xi K.
Shi, Guangpu
Li, Wei
Wang, Shusheng
Chan, Chi-Chao
author_sort Wang, Yujuan
collection PubMed
description Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis.
format Online
Article
Text
id pubmed-4730317
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-47303172016-02-11 NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration Wang, Yujuan Hanus, Jakub W. Abu-Asab, Mones S. Shen, Defen Ogilvy, Alexander Ou, Jingxing Chu, Xi K. Shi, Guangpu Li, Wei Wang, Shusheng Chan, Chi-Chao Int J Mol Sci Article Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis. MDPI 2016-01-08 /pmc/articles/PMC4730317/ /pubmed/26760997 http://dx.doi.org/10.3390/ijms17010073 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Yujuan
Hanus, Jakub W.
Abu-Asab, Mones S.
Shen, Defen
Ogilvy, Alexander
Ou, Jingxing
Chu, Xi K.
Shi, Guangpu
Li, Wei
Wang, Shusheng
Chan, Chi-Chao
NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
title NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
title_full NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
title_fullStr NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
title_full_unstemmed NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
title_short NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
title_sort nlrp3 upregulation in retinal pigment epithelium in age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730317/
https://www.ncbi.nlm.nih.gov/pubmed/26760997
http://dx.doi.org/10.3390/ijms17010073
work_keys_str_mv AT wangyujuan nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT hanusjakubw nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT abuasabmoness nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT shendefen nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT ogilvyalexander nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT oujingxing nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT chuxik nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT shiguangpu nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT liwei nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT wangshusheng nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration
AT chanchichao nlrp3upregulationinretinalpigmentepitheliuminagerelatedmaculardegeneration