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Non-Pigmented Ciliary Epithelium-Derived Extracellular Vesicles Loaded with SMAD7 siRNA Attenuate Wnt Signaling in
Saray Tabak1, Valeria Feinshtein1, Sofia Schreiber-Avissar1
1Clinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Pharmaceuticals (Basel, Switzerland)
|September 28, 2021
Summary
Non-pigmented ciliary epithelium-derived extracellular vesicles efficiently deliver anti-fibrotic siRNA to trabecular meshwork cells. This approach shows potential for treating glaucoma by lowering intraocular pressure.
Area of Science:
- Ophthalmology
- Cell Biology
- Biotechnology
Background:
- Primary open-angle glaucoma involves trabecular meshwork (TM) dysfunction, increasing resistance to aqueous humor outflow.
- Non-pigmented ciliary epithelium (NPCE) and TM cells communicate via extracellular vesicles (EVs).
Purpose of the Study:
- To investigate the potential of NPCE-derived EVs for delivering siRNA to TM cells.
- To evaluate the therapeutic efficacy of engineered EVs for glaucoma treatment.
Main Methods:
- NPCE-derived EVs were isolated and loaded with SMAD7 siRNA.
- EVs' integrity and siRNA loading were confirmed using electron microscopy and fluorescence.
- TM cells were treated with engineered EVs, and siRNA transfer was verified via qRT-PCR.
- Western blot analysis assessed protein expression changes.
Main Results:
- Engineered EVs successfully delivered siRNA into TM cells, achieving 53% mRNA knockdown of SMAD7.
- Significant elevations in β-Catenin, pGSK3β, N-Cadherin, K-Cadherin, and TGFβ2 protein levels were observed.
- NPCE-derived EVs demonstrated efficient siRNA delivery into TM cells.
Conclusions:
- NPCE-derived EVs serve as an effective vehicle for siRNA delivery to TM cells.
- This EV-mediated siRNA delivery holds promise as a novel therapeutic strategy for lowering intraocular pressure in glaucoma.
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