Astrocyte-mediated mitochondrial handling in retinal ganglion cell injury: from damaged cargo clearance to neuroinflammatory regulation and recovery responses

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Retinal ganglion cell (RGC) injury is a major feature of optic neuropathies and retinal degenerative diseases and is frequently accompanied by mitochondrial dysfunction, oxidative stress, abnormal axonal transport, and impaired mitochondrial quality control. These abnormalities are often considered primarily in the context of the intrinsic vulnerability of RGCs, which have high energetic demands and long axonal projections. RGC axons, however, are situated within a specialized glial–vascular and metabolic environment in the retinal nerve fiber layer and optic nerve head, where astrocytes, vascular structures, extracellular matrix, and local metabolic conditions contribute to neuronal homeostasis. Mitochondrial injury in RGCs therefore also needs to be considered in relation to what happens to mitochondrial material once it extends beyond cell-autonomous quality control. Here, we examine mitochondrial fate at the astrocyte–RGC interface, with particular attention to the disposal of damaged mitochondrial material, its subsequent processing within astrocytes, and its potential involvement in neuroinflammatory regulation and tissue adaptation. Mitochondrial material released from injured RGC axons can be taken up by neighboring astrocytes, where it undergoes acidification and lysosome-associated processing. If this processing capacity becomes insufficient, persistent mitochondrial components such as mtDNA may contribute to inflammatory signaling and cellular stress. In the opposite direction, functional donor mitochondria can support stressed neurons or RGC-like cells under defined experimental conditions. Together, these observations extend the study of RGC mitochondrial injury beyond the neuron itself and place astrocytic processing, mitochondrial quality control, inflammatory regulation, and metabolic adaptation within the local astrocyte–RGC interface during optic nerve injury.