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. 2021 Feb 12:16:1067-1081.
doi: 10.2147/IJN.S283164. eCollection 2021.

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

Saray Tabak  1 , Sofia Schreiber-Avissar  1 , Elie Beit-Yannai  1
Affiliations

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

Saray Tabak et al. Int J Nanomedicine. .

Abstract

Background: 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; ionic strength; non-pigmented ciliary epithelium; primary open-angle glaucoma; trabecular meshwork; zeta potential.

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Conflict of interest statement

The authors report no conflicts of interest for this work.

Figures

Figure 1
Figure 1
NPCE and TM Size and concentration.
Figure 2
Figure 2
Size Distribution of NPCE/TM/NPCE+TM – Derived EVs Suspended in PBS with Different Ionic Strengths.
Figure 3
Figure 3
Zeta Potentials of NPCE or TM – Derived EVs Suspended in Different Glaucoma eye drops and their Main Preservative.
Figure 4
Figure 4
Size Distribution of NPCE/TM – Derived EVs Suspended in Various Solutions used for Glaucoma Treatment and their Main Preservative.
Figure 5
Figure 5
Labeled NPCE EVs Uptake by TM Cells Following Exposure to Different Glaucoma eye drops and their Main Preservative.
See this image and copyright information in PMC

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