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Open Access 01-12-2024 | Glaucoma | Research

Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection

Authors: Myungjin Kim, Jun Yong Kim, Won-Kyu Rhim, Gloria Cimaglia, Andrew Want, James E. Morgan, Pete A. Williams, Chun Gwon Park, Dong Keun Han, Seungsoo Rho

Published in: Acta Neuropathologica Communications | Issue 1/2024

Abstract

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs. However, oral supplementation of drug is relatively less efficient in terms of transmissibility to RGCs compared to direct delivery methods such as intraocular injection or delivery using subconjunctival depots. Neither method is ideal, given the risks of infection and subconjunctival scarring without novel techniques. By contrast, extracellular vesicles (EVs) have advantages as a drug delivery system with low immunogeneity and tissue interactions. We have evaluated the EV delivery of NAM as an RGC protective agent using a quantitative assessment of dendritic integrity using DiOlistics, which is confirmed to be a more sensitive measure of neuronal health in our mouse glaucoma model than the evaluation of somatic loss via the immunostaining method. NAM or NAM-loaded EVs showed a significant neuroprotective effect in the mouse retinal explant model. Furthermore, NAM-loaded EVs can penetrate the sclera once deployed in the subconjunctival space. These results confirm the feasibility of using subconjunctival injection of EVs to deliver NAM to intraocular targets.

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Title: Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection
Authors: Myungjin Kim
Jun Yong Kim
Won-Kyu Rhim
Gloria Cimaglia
Andrew Want
James E. Morgan
Pete A. Williams
Chun Gwon Park
Dong Keun Han
Seungsoo Rho
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Glaucoma
Published in: Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-024-01777-0

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Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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