Figure 1.

The distinguishing metabolic features of retinal ganglion cell (RGC). RGCs are polarized into dendritic and axonal compartments that are connected to the cell body. RGC bodies are located in the ganglion cell layer (GCL). All organelles, including mitochondria within an RGC, are synthesized in the cell body and then transported to targeted sites. RGC dendrites receive inputs from bipolar cells and branch in the inner plexiform layer (IPL). Despite the unique metabolic features in the IPL, RGC dendrites primarily rely on oxidative phosphorylation (OXPHOS) for ATP and are particularly susceptible to a varied range of injuries. Dendritic arbors of the RGCs within the off sublamina of IPL are among the first to undergo shrinkage and death after very brief exposure to elevated pressure. Axons of RGCs connect the eye with the brain and are under considerable metabolic stress in both health and disease states. Mitochondria are distributed asymmetrically along optic nerve axons, with regional organelle concentrations correlating closely with the local energy demands. Mitochondrial enzyme activity and immunoreactivity are higher in these unmyelinated regions. Due to the lack of salutatory conduction, the energy demands of non-myelinated axons in the RNFL are unusually high, which renders them vulnerable to disruptions that led to energy exhaustion and eventual functional failure. The initial damage following IOP elevation is speculated to occur at the axonal compartment of the cell at the lamina cribrosa of the optic nerve head. Just posterior to scleral laminar, axons are myelinated. Myelination allows salutatory conduction of action potentials that reduces the energy demand for the cell; cytochrome c oxidase level falls precipitously in the retrobulbar optic nerve.