Vacuolar ATPase subunit Atp6v0c transgene promotes neuroprotection and long-distance axon regeneration in injured retinal ganglion neurons.

Overview

Authors: Anja Kearney¹, Agnieszka Lukomska¹, Jacob Brady¹, Ashiti Damania¹, Mahit Gupta¹, Ephraim F Trakhtenberg¹

ORCID iDs: Ephraim F Trakhtenberg

Department of Neuroscience, University of Connecticut School of Medicine, 263 Farmington Ave, Farmington, CT 06030, USA

Institutions: University of Connecticut (United States); UConn Health (United States)

Journal: Molecular therapy. Nucleic acids, volume 37, issue 2, article 102922

Dates: received 21 September 2025; accepted 27 March 2026; published online 1 April 2026

Type: Brief report · Language: English

License: CC BY

Identifiers: DOI 10.1016/j.omtn.2026.102922 · PMID 42023031 · PMCID PMC13096995 · OpenAlex W7147482023

Open access: gold, a free copy (OpenAlex)

Status: code on request

Keywords: MT: Oligonucleotides: Therapies and Applications, axon regeneration, optic nerve injury, retinal ganglion cell, gene therapy

Topic: Nerve injury and regeneration (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex

Funding: National Institutes of Health; National Eye Institute (R01-EY029739); NEI NIH HHS (R01 EY029739)

Citations: not cited yet (Europe PMC); 31 references in the paper

Abstract

Central nervous system (CNS) projection neurons’ failure to repair or regenerate injured axons has devastating consequences for those who have sustained CNS injuries. Thus, there is a need for translatable factors capable of promoting long-distance axon regeneration in the CNS. We hypothesized that supporting lysosomes in injured neurons by supplementing their structural factors through gene therapy may foster axon regeneration. To test our hypothesis, we selected Atp6v0c for experimental regulation because it plays roles in lysosomal acidification and the degradation of misfolded proteins in response to endoplasmic reticulum (ER) stress in injured neurons. We tested this in a rodent optic nerve crush (ONC) model of traumatic optic neuropathy (TON), in which injured prototypical CNS projection neurons, the retinal ganglion cells (RGCs), do not regenerate damaged axons and eventually degenerate. Atp6v0c transgene expression was achieved using intravitreally injected adeno-associated virus serotype 2 (AAV2), which transduces the RGCs. For benchmarking, we compared efficacy to AAV2 targeting of prominent regulators of axon regeneration, Pten, and Klf9. We found that Atp6v0c transgene promoted RGC survival and long-distance axon regeneration, comparable to targeting Pten and Klf9. Thus, Atp6v0c is an axon regeneration-promoting factor with potential for treating CNS injury and disease.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

geo:GSE325128, at NCBI GEO; found in “Data and code availability”

Data and code availability

The plasmid for the Atp6v0c AAV2 vector will be shared for academic purposes. This study did not generate any other new unique reagents.

RNA sequencing data from this study have been deposited in the Gene Expression Omnibus (GEO) at the NCBI repository and are publicly available (accession number GSE325128 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325128)).

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 5 keywords, 3 funders, 31 references.

Cite

This paper

Kearney, A., Lukomska, A., Brady, J., Damania, A., Gupta, M., & Trakhtenberg, E. F. (2026). Vacuolar ATPase subunit Atp6v0c transgene promotes neuroprotection and long-distance axon regeneration in injured retinal ganglion neurons. Molecular therapy. Nucleic acids, 37(2), 102922. https://doi.org/10.1016/j.omtn.2026.102922

BibTeX

@article{kearney2026vacuolar, author = {Kearney, Anja and Lukomska, Agnieszka and Brady, Jacob and Damania, Ashiti and Gupta, Mahit and Trakhtenberg, Ephraim F}, title = {{Vacuolar ATPase subunit Atp6v0c transgene promotes neuroprotection and long-distance axon regeneration in injured retinal ganglion neurons}}, journal = {Molecular therapy. Nucleic acids}, year = {2026}, month = apr, volume = {37}, number = {2}, pages = {102922}, publisher = {American Society of Gene \& Cell Therapy}, issn = {2162-2531}, doi = {10.1016/j.omtn.2026.102922}, url = {https://doi.org/10.1016/j.omtn.2026.102922}, pmid = {42023031}, pmcid = {PMC13096995} }

RIS

TY - JOUR AU - Kearney, Anja AU - Lukomska, Agnieszka AU - Brady, Jacob AU - Damania, Ashiti AU - Gupta, Mahit AU - Trakhtenberg, Ephraim F TI - Vacuolar ATPase subunit Atp6v0c transgene promotes neuroprotection and long-distance axon regeneration in injured retinal ganglion neurons T2 - Molecular therapy. Nucleic acids J2 - Mol Ther Nucleic Acids PY - 2026 DA - 2026/04/01 VL - 37 IS - 2 SP - 102922 SN - 2162-2531 PB - American Society of Gene & Cell Therapy DO - 10.1016/j.omtn.2026.102922 UR - https://doi.org/10.1016/j.omtn.2026.102922 LA - en ER -

CSL-JSON

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