Dopamine signaling from ganglion cells directs layer-specific angiogenesis in the retina

Liang, Justine H; Akhanov, Viktor; Ho, Anthony D.; Tawfik, Mohamed M.; D'Souza, Shane P; Cameron, Morven A.; Lang, Richard A.; Samuel, Melanie A.

doi:10.1016/j.cub.2023.07.040

Cited by 7 publications

(3 citation statements)

References 91 publications

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“…Furthermore, a recent study identified RGC-derived DA, which regulates retinal angiogenesis during the early postnatal period ( 57 ). However, we observed that adult RGCs did not contain TH in the retina with or without ONC, as evidenced by the lack of overlap between RBPMS and either TH immunostaining or Th-GFP signals (including displaced cells in the GCL) (fig.…”

Section: Resultsmentioning

confidence: 99%

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

Zhang,

Xue,

Tang

et al. 2024

Sci. Adv.

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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.

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Section: Resultsmentioning

confidence: 99%

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

Zhang,

Xue,

Tang

et al. 2024

Sci. Adv.

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“…However, it is unclear whether specific types of neuronal activities and neurotransmitters affect CNS vascular growth. A recent study suggested that dopaminergic activities of ganglion cells regulate retinal superficial plexus angiogenesis 69 . Cholinergic waves propagated by starburst amacrine cells have also been implicated in the development of retinal deep plexus vessels and BRB maturation 14 .…”

Section: Discussionmentioning

confidence: 99%

Glutamatergic neuronal activity regulates angiogenesis and blood-retinal barrier maturation via Norrin/β-catenin signaling

Biswas

Shahriar

Bachay

et al. 2023

Preprint

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Interactions among neuronal, glial and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Although synaptic dysfunctions precede vascular abnormalities in many retinal pathologies, how neuronal activity, specifically glutamatergic activity, regulates retinal angiogenesis and BRB maturation remains unclear. Using in vivo genetic studies in mice, single cell RNA sequencing and functional validation, we show that deep plexus angiogenesis and paracellular BRB maturation are delayed in Vglut1-/- retinas, where neurons fail to release glutamate. In contrast, deep plexus angiogenesis and paracellular BRB maturation are accelerated in Gnat1-/- retinas, where constitutively depolarized rods release excessive glutamate. Norrin mRNA expression and endothelial Norrin/β-catenin activity are downregulated in Vglut1-/- retinas, and upregulated in Gnat1-/- retinas. Pharmacological activation of endothelial Norrin/β-catenin signaling in Vglut1-/- retinas rescued defects in deep plexus angiogenesis and paracellular BRB integrity. Our findings demonstrate that glutamatergic neuronal activity regulates retinal angiogenesis and BRB maturation by modulating Norrin/β-catenin signaling.

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“…Dopamine release has been shown to significantly delay angiogenesis during wound healing, and D2 dopamine receptor antagonists significantly accelerated wound healing in mice by inducing angiogenesis, in part through its up-regulation of α5β1 integrin ( 34 ). Dopamine was also shown to inhibit vascular development in the retina by restricting VEGFR activation and Notch-Jagged1 signaling ( 35 ). GABA and its receptor signaling have also been shown to shape neurovascular interactions and angiogenesis during embryonic brain development.…”

Section: The Nervous System and Angiogenesismentioning

confidence: 99%

Involvement of neuronal factors in tumor angiogenesis and the shaping of the cancer microenvironment

Shalabi,

Belayachi,

Larrivée

2024

Front. Immunol.

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Emerging evidence suggests that nerves within the tumor microenvironment play a crucial role in regulating angiogenesis. Neurotransmitters and neuropeptides released by nerves can interact with nearby blood vessels and tumor cells, influencing their behavior and modulating the angiogenic response. Moreover, nerve-derived signals may activate signaling pathways that enhance the production of pro-angiogenic factors within the tumor microenvironment, further supporting blood vessel growth around tumors. The intricate network of communication between neural constituents and the vascular system accentuates the potential of therapeutically targeting neural-mediated pathways as an innovative strategy to modulate tumor angiogenesis and, consequently, neoplastic proliferation. Hereby, we review studies that evaluate the precise molecular interplay and the potential clinical ramifications of manipulating neural elements for the purpose of anti-angiogenic therapeutics within the scope of cancer treatment.

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Dopamine signaling from ganglion cells directs layer-specific angiogenesis in the retina

Cited by 7 publications

References 91 publications

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

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

Glutamatergic neuronal activity regulates angiogenesis and blood-retinal barrier maturation via Norrin/β-catenin signaling

Involvement of neuronal factors in tumor angiogenesis and the shaping of the cancer microenvironment

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