gms | German Medical Science

Objective: Retinal ganglion cells (RGCs) in adult people can't regenerate axon independently, leading to permanent visual loss upon injury. Recent studies suggest that presynaptic amacrine cells (ACs) participate in RGCs axon regeneration through synaptic connections. Our prior studies revealed optic nerve (ON) injury leads to increased Zn²⁺ and decreased dopamine (DA) in the retina, inhibiting RGCs survival and axon regeneration. Additionally, AR headsets may improve vision in late-stage glaucoma patients. Our studies explore Zn²⁺ and DA origins in RGC presynaptic terminals and evaluate AR aids for glaucoma visual rehabilitation.

Methods: Constructing AC and RGC-specific ZnT3 knockout mouse strains. Retinal ZnT3 and Zn²⁺ was evaluated one day post-optic nerve crush (ONC). DA synthesis in dopamine amacrine cells (DACs) and retinal DA level was measured post-ONC. L-DOPA was injected post-injury. Two weeks post-ONC, RGC survival and axon regeneration were assessed. Glaucoma patients were trained to use AR headsets, followed by assessments of visual acuity, dynamic visual field, contrast sensitivity, and search ability.

Results: ZnT3 knockout in ACs inhibited Zn²⁺ elevation post-ONC and enhanced RGC survival and axon regeneration. DA synthesis in DACs reduced post-ONC led to decreased retinal DA level. L-DOPA supplementation increased DA level, promoting RGC survival and axon regeneration. AR headsets expanded visual fields, improved contrast sensitivity and reduced search time.

Conclusions: Zn²⁺ from ACs was released into synaptic cleft through ZnT3 and DAC activity reduction results in decreased retinal DA level post-injury. Targeted ZnT3 knockout in ACs or L-DOPA supplementation both enhance RGC survival and axon regeneration. This study unveils the cellular origin of retinal Zn²⁺ after ONC and elucidates DACs' role in neural regeneration, underscoring ACs' role in ON injury. AR headsets significantly improve vision for late-stage glaucoma patients.