Spontaneous retinal waves and angiogenesis: A widefield calcium imaging perspective

Neuroplasticity in Brain Health and Disease (Newcastle University, UK) (2024) Proc Physiol Soc 57, C04

Oral Communications: Spontaneous retinal waves and angiogenesis: A widefield calcium imaging perspective

Michael Savage1, Cori Betram1, Evelyne Sernagor1,

1Newcastle University Newcastle Upon Tyne United Kingdom,

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The neonatal retina produces spontaneous waves of neural activity which propagate laterally across the ganglion cell layer, immediately underneath the developing superficial vascular plexus. Although it is speculated that early activity may guide angiogenesis, the exact relationship between these waves and the formation of the vasculature is still unclear. We have discovered an unclassified set of highly autofluorescent cell clusters (CCs) in the neonatal mouse retina. They appear under the leading edge of the vascular plexus as it expands from the optic disc to the retinal periphery as development progresses during the first postnatal week. Once the vasculature extends to the edge of the retina, these CCs completely disappear. It has been shown with large scale multielectrode array neurophysiological recordings that the origin points for retinal waves also follow a centre to periphery time course which mirrors the centrifugal development of the vasculature. To fully understand the mechanism linking these phenomena We have developed a large scale calcium imaging pipeline to study the origin of the retinal waves in relation to the distribution on CCs and the vascular plexus development. We have discovered that the majority of the wave origin points are peripheral to the vascular plexus. This leads us to believe these activity hotspots are signalling the vasculature to develop outwards from the retinal centre in order to provide oxygen to yet non-vascularised areas exhibiting metabolically demanding intense electrical activity. Our data show that one of the mechanisms by which these hotspots initiate retinal waves and signal to the angiogenic apparatus is via purinergic signalling through voltage sensitive Pannexin-1 hemichannels. Herein, we observe a reversible significant decrease in wave frequency in the presence of probenecid, a Pannexin-1 channel blocker. This further reinforces the interconnected nature of retinal development, aligning the progression of retinal waves and the expansion of the retinal vascular plexus.



Where applicable, experiments conform with Society ethical requirements.

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