The “classic” neurovascular unit consists of neurons, glia, and vascular cells. In reality, the specific players of each group will be different; therefore, the interaction and vulnerability of the system to disease will depend on the precise architecture. In the retina, neurons have been shown to stratify in specific layers or laminae.
24 Astrocytes, the glial component of the neurovascular unit in the brain, are present only at the superficial plexus of the BVs and are excluded from deeper layers. In contrast, radial glia (Müller cells) are present both at the superficial and deeper layers. Radial glia are a common feature of the developing brain. These are the first cells to develop from neural progenitors. After maturation, radial glia transform into stellate astrocytes, with the only exceptional tissue of our body, the retina. Retinal tissue consists of neurons, macroglia (including astrocytes and Müller cells), microglia, and vascular cells (including endothelial cells, pericytes, and smooth muscle cells). The neurovascular unit refers to the interactions between these cell types, which fosters an interdependence that is essential for homeostasis.
1 In the brain, astrocytes are the major type of glial cells that ensheath BVs. In the retina, this depends on the particular vascular plexus. At the superficial plexus, BVs are ensheathed by astrocytes (
Fig. 5),
25 while at the intersublaminar and deep plexuses, BVs contact Müller cells (
Fig. 6).
26 This suggests that Müller cells and astrocytes have similar roles with regard to vasculature. Indeed, it has been shown that the processes of Müller cells ensheath the vessels of the deep plexus and play a major role in the formation of the blood retinal barrier.
26 Moreover, Müller cells can express VEGF in response to hypoxia and induce the formation of deep retinal layers.
27 The neuronal composition around each retinal vascular plexus is also different. Therefore, depending on their location, vascular cells may be regulated by different neurotransmitters released from neighboring neurons. The diversity of the neurovascular unit within the retina may account for a tight control of blood flow in a tissue that lacks autonomic regulation.
4,5 This tight “on-demand” regulation may be especially important in the retina, one of the most oxygen-consuming tissues of the body.
3