Cargando…

Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment

PURPOSE: Gasdermin D (GSDMD) is crucial in neuronal pyroptosis. GSDMD-N and GSDMD-C are two subdomains of the protein GSDMD. GSDMD-N is an executor of pyroptosis, and GSDMD-C has an inhibitory effect on pyroptotic cell death. This study evaluated the role of GSDMD in photoreceptor cell pyroptosis ca...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Xiaomeng, Liu, Yang, Sun, Mengsha, Gao, Min, Li, Tong, Liang, Jian, Zhai, Yuanqi, Xu, Mengqiao, She, Xiangjun, Yang, Shiqi, Liu, Wenjia, Luo, Xueting, Sun, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425730/
https://www.ncbi.nlm.nih.gov/pubmed/32697303
http://dx.doi.org/10.1167/iovs.61.8.31
_version_ 1783570552114380800
author Li, Xiaomeng
Liu, Yang
Sun, Mengsha
Gao, Min
Li, Tong
Liang, Jian
Zhai, Yuanqi
Xu, Mengqiao
She, Xiangjun
Yang, Shiqi
Liu, Wenjia
Luo, Xueting
Sun, Xiaodong
author_facet Li, Xiaomeng
Liu, Yang
Sun, Mengsha
Gao, Min
Li, Tong
Liang, Jian
Zhai, Yuanqi
Xu, Mengqiao
She, Xiangjun
Yang, Shiqi
Liu, Wenjia
Luo, Xueting
Sun, Xiaodong
author_sort Li, Xiaomeng
collection PubMed
description PURPOSE: Gasdermin D (GSDMD) is crucial in neuronal pyroptosis. GSDMD-N and GSDMD-C are two subdomains of the protein GSDMD. GSDMD-N is an executor of pyroptosis, and GSDMD-C has an inhibitory effect on pyroptotic cell death. This study evaluated the role of GSDMD in photoreceptor cell pyroptosis caused by retinal detachment (RD). METHODS: RD models were established in rats, and GSDMD cleavage was detected by western blotting. The morphology of photoreceptors was assessed by transmission electron microscopy. Some rats were given subretinal injections of recombinant adeno-associated virus 2/8 (rAAV2/8)–GSDMD-C before RD surgery. We documented the expression of caspase-1 and GSDMD-N in retinas by western blot. Levels of IL-1β, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) were detected by quantitative RT-PCR. The membrane integrity of photoreceptors was evaluated by TOTO-3 iodide staining. Retinal function was measured by electroretinography, and the thickness of the outer nuclear layer was also recorded. We measured the activation of glial fibrillary acidic protein (GFAP), F4/80, and ionized calcium binding adaptor molecule 1 (Iba-1) by immunofluorescence. RESULTS: The cleavage of GSDMD peaked at 1 day after RD. The administration of rAAV2/8–GSDMD-C reduced the pyroptosis and subsequent apoptosis of photoreceptors and preserved the retinal function after RD. Expression of IL-1, TNF-α, and MCP-1 was decreased in the rAAV2/8–GSDMD-C group. In addition, the activation of GFAP, Iba-1, and F4/80 in retinas was alleviated by administering rAAV2/8–GSDMD-C after RD. CONCLUSIONS: GSDMD participates in the pyroptosis of photoreceptor after RD. Overexpression of GSDMD-C may block GSDMD cleavage and attenuate photoreceptor degeneration.
format Online
Article
Text
id pubmed-7425730
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The Association for Research in Vision and Ophthalmology
record_format MEDLINE/PubMed
spelling pubmed-74257302020-08-26 Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment Li, Xiaomeng Liu, Yang Sun, Mengsha Gao, Min Li, Tong Liang, Jian Zhai, Yuanqi Xu, Mengqiao She, Xiangjun Yang, Shiqi Liu, Wenjia Luo, Xueting Sun, Xiaodong Invest Ophthalmol Vis Sci Retina PURPOSE: Gasdermin D (GSDMD) is crucial in neuronal pyroptosis. GSDMD-N and GSDMD-C are two subdomains of the protein GSDMD. GSDMD-N is an executor of pyroptosis, and GSDMD-C has an inhibitory effect on pyroptotic cell death. This study evaluated the role of GSDMD in photoreceptor cell pyroptosis caused by retinal detachment (RD). METHODS: RD models were established in rats, and GSDMD cleavage was detected by western blotting. The morphology of photoreceptors was assessed by transmission electron microscopy. Some rats were given subretinal injections of recombinant adeno-associated virus 2/8 (rAAV2/8)–GSDMD-C before RD surgery. We documented the expression of caspase-1 and GSDMD-N in retinas by western blot. Levels of IL-1β, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) were detected by quantitative RT-PCR. The membrane integrity of photoreceptors was evaluated by TOTO-3 iodide staining. Retinal function was measured by electroretinography, and the thickness of the outer nuclear layer was also recorded. We measured the activation of glial fibrillary acidic protein (GFAP), F4/80, and ionized calcium binding adaptor molecule 1 (Iba-1) by immunofluorescence. RESULTS: The cleavage of GSDMD peaked at 1 day after RD. The administration of rAAV2/8–GSDMD-C reduced the pyroptosis and subsequent apoptosis of photoreceptors and preserved the retinal function after RD. Expression of IL-1, TNF-α, and MCP-1 was decreased in the rAAV2/8–GSDMD-C group. In addition, the activation of GFAP, Iba-1, and F4/80 in retinas was alleviated by administering rAAV2/8–GSDMD-C after RD. CONCLUSIONS: GSDMD participates in the pyroptosis of photoreceptor after RD. Overexpression of GSDMD-C may block GSDMD cleavage and attenuate photoreceptor degeneration. The Association for Research in Vision and Ophthalmology 2020-07-22 /pmc/articles/PMC7425730/ /pubmed/32697303 http://dx.doi.org/10.1167/iovs.61.8.31 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Retina
Li, Xiaomeng
Liu, Yang
Sun, Mengsha
Gao, Min
Li, Tong
Liang, Jian
Zhai, Yuanqi
Xu, Mengqiao
She, Xiangjun
Yang, Shiqi
Liu, Wenjia
Luo, Xueting
Sun, Xiaodong
Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment
title Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment
title_full Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment
title_fullStr Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment
title_full_unstemmed Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment
title_short Photoreceptors Degenerate Through Pyroptosis After Experimental Retinal Detachment
title_sort photoreceptors degenerate through pyroptosis after experimental retinal detachment
topic Retina
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425730/
https://www.ncbi.nlm.nih.gov/pubmed/32697303
http://dx.doi.org/10.1167/iovs.61.8.31
work_keys_str_mv AT lixiaomeng photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT liuyang photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT sunmengsha photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT gaomin photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT litong photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT liangjian photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT zhaiyuanqi photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT xumengqiao photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT shexiangjun photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT yangshiqi photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT liuwenjia photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT luoxueting photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment
AT sunxiaodong photoreceptorsdegeneratethroughpyroptosisafterexperimentalretinaldetachment