Cargando…

Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline

Retinal neurovascular injuries are a leading cause of vision loss in young adults presenting unmet therapeutic needs. Neurovascular injuries damage homeostatic communication between endothelial, pericyte, glial, and neuronal cells through signaling pathways that remain to be established. To understa...

Descripción completa

Detalles Bibliográficos
Autores principales: Colón Ortiz, Crystal, Neal, Albertine M., Avrutsky, Maria I., Choi, Monica, Smart, Jade, Lawson, Jacqueline, Troy, Carol M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643361/
https://www.ncbi.nlm.nih.gov/pubmed/36347836
http://dx.doi.org/10.1038/s41419-022-05387-3
_version_ 1784826508525699072
author Colón Ortiz, Crystal
Neal, Albertine M.
Avrutsky, Maria I.
Choi, Monica
Smart, Jade
Lawson, Jacqueline
Troy, Carol M.
author_facet Colón Ortiz, Crystal
Neal, Albertine M.
Avrutsky, Maria I.
Choi, Monica
Smart, Jade
Lawson, Jacqueline
Troy, Carol M.
author_sort Colón Ortiz, Crystal
collection PubMed
description Retinal neurovascular injuries are a leading cause of vision loss in young adults presenting unmet therapeutic needs. Neurovascular injuries damage homeostatic communication between endothelial, pericyte, glial, and neuronal cells through signaling pathways that remain to be established. To understand the mechanisms that contribute to neuronal death, we use a mouse model of retinal vein occlusion (RVO). Using this model, we previously discovered that after vascular damage, there was non-apoptotic activation of endothelial caspase-9 (EC Casp9); knock-out of EC Casp9 led to a decrease in retinal edema, capillary ischemia, and neuronal death. In this study, we aimed to explore the role of EC Casp9 in vision loss and inflammation. We found that EC Casp9 is implicated in contrast sensitivity decline, induction of inflammatory cytokines, and glial reactivity. One of the noted glial changes was increased levels of astroglial cl-caspase-6, which we found to be activated cell intrinsically by astroglial caspase-9 (Astro Casp9). Lastly, we discovered that Astro Casp9 contributes to capillary ischemia and contrast sensitivity decline after RVO (P-RVO). These findings reveal specific endothelial and astroglial non-apoptotic caspase-9 roles in inflammation and neurovascular injury respectively; and concomitant relevancy to contrast sensitivity decline.
format Online
Article
Text
id pubmed-9643361
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-96433612022-11-15 Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline Colón Ortiz, Crystal Neal, Albertine M. Avrutsky, Maria I. Choi, Monica Smart, Jade Lawson, Jacqueline Troy, Carol M. Cell Death Dis Article Retinal neurovascular injuries are a leading cause of vision loss in young adults presenting unmet therapeutic needs. Neurovascular injuries damage homeostatic communication between endothelial, pericyte, glial, and neuronal cells through signaling pathways that remain to be established. To understand the mechanisms that contribute to neuronal death, we use a mouse model of retinal vein occlusion (RVO). Using this model, we previously discovered that after vascular damage, there was non-apoptotic activation of endothelial caspase-9 (EC Casp9); knock-out of EC Casp9 led to a decrease in retinal edema, capillary ischemia, and neuronal death. In this study, we aimed to explore the role of EC Casp9 in vision loss and inflammation. We found that EC Casp9 is implicated in contrast sensitivity decline, induction of inflammatory cytokines, and glial reactivity. One of the noted glial changes was increased levels of astroglial cl-caspase-6, which we found to be activated cell intrinsically by astroglial caspase-9 (Astro Casp9). Lastly, we discovered that Astro Casp9 contributes to capillary ischemia and contrast sensitivity decline after RVO (P-RVO). These findings reveal specific endothelial and astroglial non-apoptotic caspase-9 roles in inflammation and neurovascular injury respectively; and concomitant relevancy to contrast sensitivity decline. Nature Publishing Group UK 2022-11-08 /pmc/articles/PMC9643361/ /pubmed/36347836 http://dx.doi.org/10.1038/s41419-022-05387-3 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Colón Ortiz, Crystal
Neal, Albertine M.
Avrutsky, Maria I.
Choi, Monica
Smart, Jade
Lawson, Jacqueline
Troy, Carol M.
Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline
title Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline
title_full Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline
title_fullStr Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline
title_full_unstemmed Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline
title_short Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline
title_sort neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643361/
https://www.ncbi.nlm.nih.gov/pubmed/36347836
http://dx.doi.org/10.1038/s41419-022-05387-3
work_keys_str_mv AT colonortizcrystal neurovascularinjuryassociatednonapoptoticendothelialcaspase9andastroglialcaspase9mediateinflammationandcontrastsensitivitydecline
AT nealalbertinem neurovascularinjuryassociatednonapoptoticendothelialcaspase9andastroglialcaspase9mediateinflammationandcontrastsensitivitydecline
AT avrutskymariai neurovascularinjuryassociatednonapoptoticendothelialcaspase9andastroglialcaspase9mediateinflammationandcontrastsensitivitydecline
AT choimonica neurovascularinjuryassociatednonapoptoticendothelialcaspase9andastroglialcaspase9mediateinflammationandcontrastsensitivitydecline
AT smartjade neurovascularinjuryassociatednonapoptoticendothelialcaspase9andastroglialcaspase9mediateinflammationandcontrastsensitivitydecline
AT lawsonjacqueline neurovascularinjuryassociatednonapoptoticendothelialcaspase9andastroglialcaspase9mediateinflammationandcontrastsensitivitydecline
AT troycarolm neurovascularinjuryassociatednonapoptoticendothelialcaspase9andastroglialcaspase9mediateinflammationandcontrastsensitivitydecline