Dynamic changes in cell size and corresponding cell fate after optic nerve injury

Abstract Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in v...

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Autores principales:	Benjamin M. Davis, Li Guo, Nivedita Ravindran, Ehtesham Shamsher, Veerle Baekelandt, Hannah Mitchell, Anil A. Bharath, Lies De Groef, M. Francesca Cordeiro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08eac2c76a8646a3ae3dcc3c2431dae3
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spelling	oai:doaj.org-article:08eac2c76a8646a3ae3dcc3c2431dae32021-12-02T12:33:05ZDynamic changes in cell size and corresponding cell fate after optic nerve injury10.1038/s41598-020-77760-12045-2322https://doaj.org/article/08eac2c76a8646a3ae3dcc3c2431dae32020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77760-1https://doaj.org/toc/2045-2322Abstract Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.Benjamin M. DavisLi GuoNivedita RavindranEhtesham ShamsherVeerle BaekelandtHannah MitchellAnil A. BharathLies De GroefM. Francesca CordeiroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin M. Davis Li Guo Nivedita Ravindran Ehtesham Shamsher Veerle Baekelandt Hannah Mitchell Anil A. Bharath Lies De Groef M. Francesca Cordeiro Dynamic changes in cell size and corresponding cell fate after optic nerve injury
description	Abstract Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.
format	article
author	Benjamin M. Davis Li Guo Nivedita Ravindran Ehtesham Shamsher Veerle Baekelandt Hannah Mitchell Anil A. Bharath Lies De Groef M. Francesca Cordeiro
author_facet	Benjamin M. Davis Li Guo Nivedita Ravindran Ehtesham Shamsher Veerle Baekelandt Hannah Mitchell Anil A. Bharath Lies De Groef M. Francesca Cordeiro
author_sort	Benjamin M. Davis
title	Dynamic changes in cell size and corresponding cell fate after optic nerve injury
title_short	Dynamic changes in cell size and corresponding cell fate after optic nerve injury
title_full	Dynamic changes in cell size and corresponding cell fate after optic nerve injury
title_fullStr	Dynamic changes in cell size and corresponding cell fate after optic nerve injury
title_full_unstemmed	Dynamic changes in cell size and corresponding cell fate after optic nerve injury
title_sort	dynamic changes in cell size and corresponding cell fate after optic nerve injury
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/08eac2c76a8646a3ae3dcc3c2431dae3
work_keys_str_mv	AT benjaminmdavis dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT liguo dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT niveditaravindran dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT ehteshamshamsher dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT veerlebaekelandt dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT hannahmitchell dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT anilabharath dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT liesdegroef dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury AT mfrancescacordeiro dynamicchangesincellsizeandcorrespondingcellfateafteropticnerveinjury
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Dynamic changes in cell size and corresponding cell fate after optic nerve injury

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