Glaucoma-associated Optineurin mutations increase transcellular degradation of mitochondria in a vertebrate optic nerve
- University of California, Davis, United States
- Stanford University, United States
- University of California, San Diego, United States
Abstract
We previously described a process whereby mitochondria shed by retinal ganglion cell (RGC) axons are transferred to and degraded by surrounding astrocytes in the optic nerve head of mice. Since the mitophagy receptor Optineurin (OPTN) is one of few large-effect glaucoma genes and axonal damage occurs at the optic nerve head in glaucoma, here we explored whether OPTN mutations perturb the transcellular degradation of mitochondria. Live-imaging of Xenopus laevis optic nerves revealed that diverse human mutant but not wildtype OPTN increase stationary mitochondria and mitophagy machinery and their colocalization within, and in the case of the glaucoma-associated OPTN mutations also outside of, RGC axons. These extra-axonal mitochondria are degraded by astrocytes. Our studies demonstrate that expression of OPTN carrying a glaucoma-associated mutation results in increased transcellular degradation of axonal mitochondria.
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Article and author information
Author details
Nicholas Marsh-Armstrong
Funding
National Eye Institute (EY026471)
- Nicholas Marsh-Armstrong
National Eye Institute (EY029087)
- Nicholas Marsh-Armstrong
National Eye Institute (P30-EY012576)
- Nicholas Marsh-Armstrong
National Institutes of Health (U24 NS120055)
- Nicholas Marsh-Armstrong
National Institutes of Health (ISI0OD021784)
- Nicholas Marsh-Armstrong
National Institutes of Health (GM82949)
- Nicholas Marsh-Armstrong
National Science Foundation (2014862-UTA20-000)
- Nicholas Marsh-Armstrong
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The study was carried out in accordance with recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal work was carried out according to approved institutional care and use committee protocols (#22908) of the University of California Davis. Surgeries and imaging were carried out under MS-222 anesthesia and all efforts were made to minimize pain or distress to the animals.
Copyright
© 2025, Jeong et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Glaucoma-associated Optineurin mutations increase transcellular degradation of mitochondria in a vertebrate optic nerve
eLife 14:e103844.
https://doi.org/10.7554/eLife.103844
