Durmaz, Esmahan, Trabzonlu, Kubra, Esmaeili, Maryam, Nehme, Hanady, Alverez-Erviti, Lydia, Syed, Yasir Ahmed  ORCID: https://orcid.org/0000-0001-9495-307X, Clayton, Aled ORCID: https://orcid.org/0000-0002-3087-9226 and Mead, Ben ORCID: https://orcid.org/0000-0001-5855-0097
2026.
Extracellular vesicle–mediated delivery of miR-181a-3p confers neuroprotection to degenerating retinal ganglion cells.
Experimental Eye Research
, 110882.
10.1016/j.exer.2026.110882
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Abstract
Background: Glaucoma is a progressive optic neuropathy marked by the irreversible degeneration of retinal ganglion cells (RGCs), leading to vision loss. RGC injury is also central to other optic and neurodegenerative conditions, including traumatic optic neuropathy. Purpose: We evaluated whether extracellular vesicles (EVs) derived from retinal precursor cells could serve as an effective platform for the delivery of neuroprotective microRNAs (miRNAs), focusing on miR-181a-3p, to preserve RGC viability and function. Methods: Based on prior profiling of miRNAs differentially expressed in injured RGCs, four candidate miRNAs were screened for neuroprotective effects in primary rat retinal cultures and human embryonic stem cell–derived RGCs. miR-181a-3p, which showed the strongest preservation of RGC survival, was selected for further study. EVs were isolated from R-28 retinal precursor cells, loaded with miR-181a-3p via electroporation, and characterized for particle size, charge, and loading efficiency. EV uptake and neuroprotective efficacy were evaluated in vitro by fluorescence imaging, qPCR, and Ca2+-activity assays, and in vivo by intravitreal injection of labelled EVs to assess retinal distribution and cellular uptake. Results: EV-mediated delivery of miR-181a-3p enhanced RGC survival and preserved intracellular Ca2+ dynamics compared to free miRNA or lipofectamine-based transfection. EVs improved miRNA stability, enabled selective targeting of retinal cell types, and partially modulated the p38/MAPK signalling axis. EV loading also improved the delivery of miRNA to the retina in vivo. Conclusion: Our findings demonstrate that EVs offer a biocompatible, cell-specific, and functionally effective platform for miRNA delivery to the retina. EV-based administration of miR-181a-3p may represent a novel neuroprotective strategy for glaucoma and related optic neuropathies.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | In Press |
| Schools: | Schools > Optometry and Vision Sciences Schools > Medicine Schools > Biosciences |
| Publisher: | Elsevier BV |
| ISSN: | 0014-4835 |
| Date of First Compliant Deposit: | 26 January 2026 |
| Date of Acceptance: | 21 January 2026 |
| Last Modified: | 26 Jan 2026 14:16 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/184178 |
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