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OptoDrum

Publication

March 11, 2025 • ✎ STRIA TECH

Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function

Topics:

CNS Trauma and Acute Injury: TBI, Optic Nerve Injury, Stroke

Glaucoma

Maintaining and Restoring Vision

Optic Nerve Damage

The Optic Nerve, its Neurons and Diseases

Publication

Science Advances (Aug 02, 2024) Modulating amacrine cell-derived dopamine signaling promotes optic nerve regeneration and preserves visual function

Zhang Q, Xue J, Tang J, Wu S, Liu Z, Wu C, Liu C, Liu Y, Lin J, Han J, Liu L, Chen Y, Yang J, Li Z, Zhao L, Wei Y, Li Y, Zhuo Y

DOI: 10.1126/sciadv.ado0866 >>

This study explores a novel approach to optic nerve regeneration by manipulating interactions between amacrine cells and retinal ganglion cells. Researchers identified dopaminergic amacrine cells that respond to optic nerve injury by reducing activity and dopamine release. Activating these dopaminergic amacrine cells or increasing dopamine release showed neuroprotective effects and modest axon regeneration. The study pinpointed the dopamine receptor D1 as a key mediator, demonstrating that overexpression of ganglion cell-specific dopamine receptor D1 significantly improved ganglion cell survival and axon regeneration after injury, while also preserving visual function in a glaucoma model, as demonstrated by optomotor measurements with the OptoDrum and other visually guided behaviors.

As part of the central nervous system, the optic nerve, composed of axons from retinal ganglion cells (RGCs), generally fails to regenerate on its own when injured in adult mammals. An innovative approach to promoting optic nerve regeneration involves manipulating the interactions between amacrine cells (ACs) and RGCs. Here, we identified a unique AC subtype, dopaminergic ACs (DACs), that responded early after optic nerve crush by down-regulating neuronal activity and reducing retinal dopamine (DA) release. Activating DACs or augmenting DA release with levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. Within this context, we pinpointed the DA receptor D1 (DRD1) as a critical mediator of DAC-derived DA and showed that RGC-specific Drd1 overexpression effectively overcame subtype-specific barriers to regeneration. This strategy markedly boosted RGC survival and axon regeneration after crush and preserved vision in a glaucoma model. This study unveils the crucial role of DAC-derived DA signaling in optic nerve regeneration, holding promise for therapeutic insights into neural repair.