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Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment

After retinal detachment (RD), the induction of autophagy protects photoreceptors (PR) from apoptotic cell death. The cytoplasmic high-mobility group box 1 (HMGB1) promotes autophagy. We previously demonstrated that the deletion of HMGB1 from rod PRs results in a more rapid death of these cells afte...

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Autores principales: Ross, Bing X., Jia, Lin, Kong, Dejuan, Wang, Tiantian, Hager, Heather M., Abcouwer, Steven F., Zacks, David N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394251/
https://www.ncbi.nlm.nih.gov/pubmed/34440779
http://dx.doi.org/10.3390/cells10082010
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author Ross, Bing X.
Jia, Lin
Kong, Dejuan
Wang, Tiantian
Hager, Heather M.
Abcouwer, Steven F.
Zacks, David N.
author_facet Ross, Bing X.
Jia, Lin
Kong, Dejuan
Wang, Tiantian
Hager, Heather M.
Abcouwer, Steven F.
Zacks, David N.
author_sort Ross, Bing X.
collection PubMed
description After retinal detachment (RD), the induction of autophagy protects photoreceptors (PR) from apoptotic cell death. The cytoplasmic high-mobility group box 1 (HMGB1) promotes autophagy. We previously demonstrated that the deletion of HMGB1 from rod PRs results in a more rapid death of these cells after RD. In this work, we tested the hypothesis that the lack of HMGB1 accelerates PR death after RD due to the reduced activation of protective autophagy in the retina after RD. The injection of 1% hyaluronic acid into the subretinal space was used to create acute RD in mice with a rhodopsin-Cre-mediated conditional knockout (cKO) of HMGB1 in rods (HMGB1Δrod) and littermate controls. RD sharply increased the number of apoptotic cells in the outer nuclear layer (ONL), and this number was further increased in HMGB1Δrod mouse retinas. The activation of autophagy after RD was reduced in the HMGB1Δrod mouse retinas compared to controls, as evidenced by diminished levels of autophagy regulatory proteins LC3-II, Beclin1, ATG5/12, and phospho-ATG16L1. The cKO of HMGB1 in rods increased the expression of Fas and the Bax/Bcl-2 ratio in detached retinas, promoting apoptotic cell death. In conclusion, endogenous HMGB1 facilitates autophagy activation in PR cells following RD to promote PR cell survival and reduce programmed apoptotic cell death.
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spelling pubmed-83942512021-08-28 Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment Ross, Bing X. Jia, Lin Kong, Dejuan Wang, Tiantian Hager, Heather M. Abcouwer, Steven F. Zacks, David N. Cells Article After retinal detachment (RD), the induction of autophagy protects photoreceptors (PR) from apoptotic cell death. The cytoplasmic high-mobility group box 1 (HMGB1) promotes autophagy. We previously demonstrated that the deletion of HMGB1 from rod PRs results in a more rapid death of these cells after RD. In this work, we tested the hypothesis that the lack of HMGB1 accelerates PR death after RD due to the reduced activation of protective autophagy in the retina after RD. The injection of 1% hyaluronic acid into the subretinal space was used to create acute RD in mice with a rhodopsin-Cre-mediated conditional knockout (cKO) of HMGB1 in rods (HMGB1Δrod) and littermate controls. RD sharply increased the number of apoptotic cells in the outer nuclear layer (ONL), and this number was further increased in HMGB1Δrod mouse retinas. The activation of autophagy after RD was reduced in the HMGB1Δrod mouse retinas compared to controls, as evidenced by diminished levels of autophagy regulatory proteins LC3-II, Beclin1, ATG5/12, and phospho-ATG16L1. The cKO of HMGB1 in rods increased the expression of Fas and the Bax/Bcl-2 ratio in detached retinas, promoting apoptotic cell death. In conclusion, endogenous HMGB1 facilitates autophagy activation in PR cells following RD to promote PR cell survival and reduce programmed apoptotic cell death. MDPI 2021-08-06 /pmc/articles/PMC8394251/ /pubmed/34440779 http://dx.doi.org/10.3390/cells10082010 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ross, Bing X.
Jia, Lin
Kong, Dejuan
Wang, Tiantian
Hager, Heather M.
Abcouwer, Steven F.
Zacks, David N.
Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment
title Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment
title_full Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment
title_fullStr Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment
title_full_unstemmed Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment
title_short Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment
title_sort conditional knock out of high-mobility group box 1 (hmgb1) in rods reduces autophagy activation after retinal detachment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394251/
https://www.ncbi.nlm.nih.gov/pubmed/34440779
http://dx.doi.org/10.3390/cells10082010
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