Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension

Abstract Autophagy is an essential cellular process for the degradation and recycling of cellular components, and its dysregulation has been linked to neuronal cell death and neurodegeneration. In glaucoma, the role of autophagy in retinal ganglion cell (RGC) survival remains contradictory. Moreover...

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Autores principales:	Si Hyung Lee, Kyung Sun Shim, Chan Yun Kim, Tae Kwann Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0623781d2a734418ab85608319562015
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spelling	oai:doaj.org-article:0623781d2a734418ab856083195620152021-12-02T15:53:59ZCharacterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension10.1038/s41598-021-85181-x2045-2322https://doaj.org/article/0623781d2a734418ab856083195620152021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85181-xhttps://doaj.org/toc/2045-2322Abstract Autophagy is an essential cellular process for the degradation and recycling of cellular components, and its dysregulation has been linked to neuronal cell death and neurodegeneration. In glaucoma, the role of autophagy in retinal ganglion cell (RGC) survival remains contradictory. Moreover, the effects of autophagy modulation at different time-points on RGC survival in a glaucoma model have not been investigated. In this study, we assessed the time-dependent role of autophagy in RGC survival in a circumlimbal suture-induced ocular hypertensive (OHT) rat model. Intraocular pressure (IOP) elevation led to a gradual autophagy induction, which reached a maximum between 1 and 4 weeks after OHT induction. On the other hand, early autophagy was impaired between 1 and 3 days after circumlimbal suturing, indicated by increased p62 levels due to reduced autophagosomal turnover. The intravitreal administration of rapamycin at different time-points after the application of the circumlimbal suture indicated that autophagy induction early during OHT development had potent survival-promoting effects in RGCs. In conclusion, our findings suggest that the role of autophagy in RGCs during OHT development might differ in a time-dependent manner. Modulating autophagy at the appropriate time might serve as a potential therapeutic approach to enhance RGC survival in OHT.Si Hyung LeeKyung Sun ShimChan Yun KimTae Kwann ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Si Hyung Lee Kyung Sun Shim Chan Yun Kim Tae Kwann Park Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension
description	Abstract Autophagy is an essential cellular process for the degradation and recycling of cellular components, and its dysregulation has been linked to neuronal cell death and neurodegeneration. In glaucoma, the role of autophagy in retinal ganglion cell (RGC) survival remains contradictory. Moreover, the effects of autophagy modulation at different time-points on RGC survival in a glaucoma model have not been investigated. In this study, we assessed the time-dependent role of autophagy in RGC survival in a circumlimbal suture-induced ocular hypertensive (OHT) rat model. Intraocular pressure (IOP) elevation led to a gradual autophagy induction, which reached a maximum between 1 and 4 weeks after OHT induction. On the other hand, early autophagy was impaired between 1 and 3 days after circumlimbal suturing, indicated by increased p62 levels due to reduced autophagosomal turnover. The intravitreal administration of rapamycin at different time-points after the application of the circumlimbal suture indicated that autophagy induction early during OHT development had potent survival-promoting effects in RGCs. In conclusion, our findings suggest that the role of autophagy in RGCs during OHT development might differ in a time-dependent manner. Modulating autophagy at the appropriate time might serve as a potential therapeutic approach to enhance RGC survival in OHT.
format	article
author	Si Hyung Lee Kyung Sun Shim Chan Yun Kim Tae Kwann Park
author_facet	Si Hyung Lee Kyung Sun Shim Chan Yun Kim Tae Kwann Park
author_sort	Si Hyung Lee
title	Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension
title_short	Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension
title_full	Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension
title_fullStr	Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension
title_full_unstemmed	Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension
title_sort	characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0623781d2a734418ab85608319562015
work_keys_str_mv	AT sihyunglee characterizationoftheroleofautophagyinretinalganglioncellsurvivalovertimeusingaratmodelofchronicocularhypertension AT kyungsunshim characterizationoftheroleofautophagyinretinalganglioncellsurvivalovertimeusingaratmodelofchronicocularhypertension AT chanyunkim characterizationoftheroleofautophagyinretinalganglioncellsurvivalovertimeusingaratmodelofchronicocularhypertension AT taekwannpark characterizationoftheroleofautophagyinretinalganglioncellsurvivalovertimeusingaratmodelofchronicocularhypertension
_version_	1718385491727876096

Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension

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