
Glaucoma-associated mutations in the mitophagy receptor Optineurin (OPTN) increase the fraction of stationary mitochondria, OPTN, and LC3b within retinal ganglion cell (RGC) axons, as well as the shedding of mitochondria from axons and their subsequent degradation by surrounding astrocytes.


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We previously described a process referred to as transmitophagy where 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 transmitophagy. 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 support the view that in RGC axons under baseline conditions there are low levels of mitophagy, but that glaucoma-associated perturbations in OPTN result in increased axonal mitophagy involving the shedding and astrocytic degradation of the mitochondria.

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### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

Glaucoma-associated Optineurin mutations increase transmitophagy in a vertebrate optic nerve

glaucoma-associated-optineurin-mutations-increase-axonal-mitophagy-and-shedding-of-mitochondria-in-a-vertebrate-optic-nerve-model


Glaucoma-associated Optineurin Mutations Increase Axonal Mitophagy and Shedding of Mitochondria in a Vertebrate Optic Nerve Model
