Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells

Saray Tabak, Sofia Schreiber-Avissar, Elie Beit-Yannai Clinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, Beer-Sheva, IsraelCorrespondence: Elie Beit-YannaiClinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, POB 653, Beer-Sheva,...

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Autores principales:	Tabak S, Schreiber-Avissar S, Beit-Yannai E
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	extracellular vesicles trabecular meshwork non-pigmented ciliary epithelium primary open angle glaucoma zeta potential ionic strength Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/244c6b5084964e8cbdaf23b9aba41672
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spelling	oai:doaj.org-article:244c6b5084964e8cbdaf23b9aba416722021-12-02T14:39:24ZInfluence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells1178-2013https://doaj.org/article/244c6b5084964e8cbdaf23b9aba416722021-02-01T00:00:00Zhttps://www.dovepress.com/influence-of-anti-glaucoma-drugs-on-uptake-of-extracellular-vesicles-b-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Saray Tabak, Sofia Schreiber-Avissar, Elie Beit-Yannai Clinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, Beer-Sheva, IsraelCorrespondence: Elie Beit-YannaiClinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, POB 653, Beer-Sheva, 84105, IsraelTel +972-8-6477374Fax +972-8-6479303Email bye@bgu.ac.ilBackground: Extracellular vesicles (EVs) are capable of manipulating cellular functions for the maintenance of biological homeostasis and disease progression, such as in glaucoma disease. These nano-particles carry a net negative surface charge under physiological conditions that can contribute to EVs:EVs interaction and their uptake by target cells.Purpose: To investigate the effect of glaucoma drugs on EVs physicochemical characters and the implications for their uptake by trabecular meshwork (TM) cells.Methods: TM or non-pigmented ciliary epithelium (NPCE) cells derived EVs were incubated with commercial anti-glaucoma formulation, Timolol maleate, Brinzolamide or Benzalkonium Cl and their size and zeta potential (ZP) and physical interactions of EVs derived from NPCE cells and TM cells were evaluated. The contribution of EVs interactions to up-take by TM cells was examined using fluorescence-activated cell sorting.Results: EVs size and ZP were affected by the ionic strength of the buffer rather than EVs type. Commercial glaucoma eye drops, including β-blocker, α-2-agonist and prostaglandin analogs, reduced NPCE EVs ZP, whereas exposure of EVs to carbonic anhydrase inhibitor caused an increase in the ZP. A correlation was found between increased ZP values and increased NPCE EVs uptake by TM cells. We were able to show that Benzalkonium chloride stands behind this ZP effect and not Timolol or Brinzolamide.Conclusion: Altogether, our findings demonstrate that EVs size, surface membrane charge, and ionic strength of the surrounding have an impact on EVs:EVs interactions, which affect the uptake of NPCE EVs by TM cells.Keywords: extracellular vesicles, trabecular meshwork, non-pigmented ciliary epithelium, primary open-angle glaucoma, zeta potential, ionic strengthTabak SSchreiber-Avissar SBeit-Yannai EDove Medical Pressarticleextracellular vesiclestrabecular meshworknon-pigmented ciliary epitheliumprimary open angle glaucomazeta potentialionic strengthMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1067-1081 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular vesicles trabecular meshwork non-pigmented ciliary epithelium primary open angle glaucoma zeta potential ionic strength Medicine (General) R5-920
spellingShingle	extracellular vesicles trabecular meshwork non-pigmented ciliary epithelium primary open angle glaucoma zeta potential ionic strength Medicine (General) R5-920 Tabak S Schreiber-Avissar S Beit-Yannai E Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells
description	Saray Tabak, Sofia Schreiber-Avissar, Elie Beit-Yannai Clinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, Beer-Sheva, IsraelCorrespondence: Elie Beit-YannaiClinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, POB 653, Beer-Sheva, 84105, IsraelTel +972-8-6477374Fax +972-8-6479303Email bye@bgu.ac.ilBackground: Extracellular vesicles (EVs) are capable of manipulating cellular functions for the maintenance of biological homeostasis and disease progression, such as in glaucoma disease. These nano-particles carry a net negative surface charge under physiological conditions that can contribute to EVs:EVs interaction and their uptake by target cells.Purpose: To investigate the effect of glaucoma drugs on EVs physicochemical characters and the implications for their uptake by trabecular meshwork (TM) cells.Methods: TM or non-pigmented ciliary epithelium (NPCE) cells derived EVs were incubated with commercial anti-glaucoma formulation, Timolol maleate, Brinzolamide or Benzalkonium Cl and their size and zeta potential (ZP) and physical interactions of EVs derived from NPCE cells and TM cells were evaluated. The contribution of EVs interactions to up-take by TM cells was examined using fluorescence-activated cell sorting.Results: EVs size and ZP were affected by the ionic strength of the buffer rather than EVs type. Commercial glaucoma eye drops, including β-blocker, α-2-agonist and prostaglandin analogs, reduced NPCE EVs ZP, whereas exposure of EVs to carbonic anhydrase inhibitor caused an increase in the ZP. A correlation was found between increased ZP values and increased NPCE EVs uptake by TM cells. We were able to show that Benzalkonium chloride stands behind this ZP effect and not Timolol or Brinzolamide.Conclusion: Altogether, our findings demonstrate that EVs size, surface membrane charge, and ionic strength of the surrounding have an impact on EVs:EVs interactions, which affect the uptake of NPCE EVs by TM cells.Keywords: extracellular vesicles, trabecular meshwork, non-pigmented ciliary epithelium, primary open-angle glaucoma, zeta potential, ionic strength
format	article
author	Tabak S Schreiber-Avissar S Beit-Yannai E
author_facet	Tabak S Schreiber-Avissar S Beit-Yannai E
author_sort	Tabak S
title	Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells
title_short	Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells
title_full	Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells
title_fullStr	Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells
title_full_unstemmed	Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells
title_sort	influence of anti-glaucoma drugs on uptake of extracellular vesicles by trabecular meshwork cells
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/244c6b5084964e8cbdaf23b9aba41672
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Influence of Anti-Glaucoma Drugs on Uptake of Extracellular Vesicles by Trabecular Meshwork Cells

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