A neurobiology perspective on the assembly of retinal vasculature from 2D to 3D

The reciprocal regulation of the neural ensemble and vascular network within the mammalian central nervous system (CNS) is crucial for its development and functionality. Neuron-derived pro-angiogenic factors, such as growth factors, morphogens, and guidance cues, play a key role in forming stereotypical vascular architectures in the cortex, spinal cord, and cerebellum during development. Notably, the CNS vasculature forms distinct 3D lattice structures composed of laminar vascular networks interconnected by penetrating vessels. This contrasts with the more random 3D arborizations found in tumors. While the morphogen gradients for vascular network growth have been well-studied, the mechanisms contributing to vascular patterning and lattice maintenance in 3D are not fully understood. The mammalian retina provides an ideal model for studying these mechanisms, given its laminar organization of neurons and plexus organization of vessels, allowing for the investigation of 2D growth to 3D lattice establishment in a stepwise manner. Notably, recent studies have highlighted the roles of neurons and glia in retinal vascular patterning in 2D, as well as the involvement of neurotransmitters in regulating vascular growth. Additionally, direct neuron-to-vessel interactions have been found to contribute to 3D retinal vascular lattice formation. As emerging technologies provide new insights into retinal vascular assembly in 3D, understanding the developmental regulation and the physiological and pathophysiological effects of 3D lattice disruption remains a fertile field of research.