Evaluating the neuroprotective impact of senolytic drugs on human vision

Abstract Glaucoma, a chronic neurodegenerative disease of retinal ganglion cells (RGCs), is a leading cause of irreversible blindness worldwide. Its management currently focuses on lowering intraocular pressure to slow disease progression. However, disease-modifying, neuroprotective treatments for g...

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Autores principales:	Nevin W. El-Nimri, Spencer M. Moore, Linda M. Zangwill, James A. Proudfoot, Robert N. Weinreb, Dorota Skowronska-Krawczyk, Sally L. Baxter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c1aad6bcbf894135b674b4437693f52f
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spelling	oai:doaj.org-article:c1aad6bcbf894135b674b4437693f52f2021-12-02T15:11:52ZEvaluating the neuroprotective impact of senolytic drugs on human vision10.1038/s41598-020-78802-42045-2322https://doaj.org/article/c1aad6bcbf894135b674b4437693f52f2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78802-4https://doaj.org/toc/2045-2322Abstract Glaucoma, a chronic neurodegenerative disease of retinal ganglion cells (RGCs), is a leading cause of irreversible blindness worldwide. Its management currently focuses on lowering intraocular pressure to slow disease progression. However, disease-modifying, neuroprotective treatments for glaucoma remain a major unmet need. Recently, senescent cells have been observed in glaucomatous eyes, exposing a potential pathway for alternative glaucoma therapies. Prior studies demonstrated that targeting senescent RGCs for removal (i.e., a senolytic approach) protected healthy RGCs and preserved visual function in a mouse ocular hypertension model. However, the effects of senolytic drugs on vision in human patients are unknown. Here, we used existing clinical data to conduct a retrospective cohort study in 28 human glaucoma patients who had been exposed to senolytics. Senolytic exposure was not associated with decreased visual acuity, elevated intraocular pressure, or documentation of senolytic-related adverse ocular effects by treating ophthalmologists. Additionally, patients exposed to senolytics (n = 9) did not exhibit faster progression of glaucomatous visual field damage compared to matched glaucoma patients (n = 26) without senolytic exposure. These results suggest that senolytic drugs do not carry significant ocular toxicity and provide further support for additional evaluation of the potential neuroprotective effects of senolytics on glaucoma and other neurodegenerative diseases.Nevin W. El-NimriSpencer M. MooreLinda M. ZangwillJames A. ProudfootRobert N. WeinrebDorota Skowronska-KrawczykSally L. BaxterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nevin W. El-Nimri Spencer M. Moore Linda M. Zangwill James A. Proudfoot Robert N. Weinreb Dorota Skowronska-Krawczyk Sally L. Baxter Evaluating the neuroprotective impact of senolytic drugs on human vision
description	Abstract Glaucoma, a chronic neurodegenerative disease of retinal ganglion cells (RGCs), is a leading cause of irreversible blindness worldwide. Its management currently focuses on lowering intraocular pressure to slow disease progression. However, disease-modifying, neuroprotective treatments for glaucoma remain a major unmet need. Recently, senescent cells have been observed in glaucomatous eyes, exposing a potential pathway for alternative glaucoma therapies. Prior studies demonstrated that targeting senescent RGCs for removal (i.e., a senolytic approach) protected healthy RGCs and preserved visual function in a mouse ocular hypertension model. However, the effects of senolytic drugs on vision in human patients are unknown. Here, we used existing clinical data to conduct a retrospective cohort study in 28 human glaucoma patients who had been exposed to senolytics. Senolytic exposure was not associated with decreased visual acuity, elevated intraocular pressure, or documentation of senolytic-related adverse ocular effects by treating ophthalmologists. Additionally, patients exposed to senolytics (n = 9) did not exhibit faster progression of glaucomatous visual field damage compared to matched glaucoma patients (n = 26) without senolytic exposure. These results suggest that senolytic drugs do not carry significant ocular toxicity and provide further support for additional evaluation of the potential neuroprotective effects of senolytics on glaucoma and other neurodegenerative diseases.
format	article
author	Nevin W. El-Nimri Spencer M. Moore Linda M. Zangwill James A. Proudfoot Robert N. Weinreb Dorota Skowronska-Krawczyk Sally L. Baxter
author_facet	Nevin W. El-Nimri Spencer M. Moore Linda M. Zangwill James A. Proudfoot Robert N. Weinreb Dorota Skowronska-Krawczyk Sally L. Baxter
author_sort	Nevin W. El-Nimri
title	Evaluating the neuroprotective impact of senolytic drugs on human vision
title_short	Evaluating the neuroprotective impact of senolytic drugs on human vision
title_full	Evaluating the neuroprotective impact of senolytic drugs on human vision
title_fullStr	Evaluating the neuroprotective impact of senolytic drugs on human vision
title_full_unstemmed	Evaluating the neuroprotective impact of senolytic drugs on human vision
title_sort	evaluating the neuroprotective impact of senolytic drugs on human vision
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/c1aad6bcbf894135b674b4437693f52f
work_keys_str_mv	AT nevinwelnimri evaluatingtheneuroprotectiveimpactofsenolyticdrugsonhumanvision AT spencermmoore evaluatingtheneuroprotectiveimpactofsenolyticdrugsonhumanvision AT lindamzangwill evaluatingtheneuroprotectiveimpactofsenolyticdrugsonhumanvision AT jamesaproudfoot evaluatingtheneuroprotectiveimpactofsenolyticdrugsonhumanvision AT robertnweinreb evaluatingtheneuroprotectiveimpactofsenolyticdrugsonhumanvision AT dorotaskowronskakrawczyk evaluatingtheneuroprotectiveimpactofsenolyticdrugsonhumanvision AT sallylbaxter evaluatingtheneuroprotectiveimpactofsenolyticdrugsonhumanvision
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Evaluating the neuroprotective impact of senolytic drugs on human vision

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