Investigation of heterocellular features of the mouse retinal neurovascular unit by 3D electron microscopy

Abstract

The retina has a complex structure with a diverse collection of component cells that work together to facilitate vision. The retinal capillaries supplying the nutritional requirements to the inner retina have an intricate system of neural, glial and vascular elements that interconnect to form the neurovascular unit (NVU). The retina has no autonomic nervous system and so relies on the NVU as an interdependent, physical

The retina’s neurovascular unit: Müller glial sheaths and neuronal contacts

“…In this volume, the SVP was covered virtually completely by Müller and astrocytic glial processes, consistent with a recent report (Albargothy et al, 2023). However, we did identify two small gaps in the glial sheath where the SVP vessel was contacted by neurons ((Figures 4A, B-C top and S4A).…”

“…We examined publicly available SBFSEM datasets of C57/Bl6 mouse retina (Ding et al, 2016; Helmstaedter et al, 2013; Pallotto et al, 2015) to visualize glial ensheathment of retinal vessels at unprecedented resolution and scale. Our study builds upon an earlier SEM analysis in mouse retina focused on astrocytic sheathes in the SVP (Albargothy et al, 2023). We focused mainly on the IVP and DVP, where Müller cells rather than astrocytes wrap the capillaries.…”

“…In the central nervous system, capillaries and pericytes are ensheathed by glial endfeet. In the brain, the endfeet derive from astrocytes (Mathiisen et al, 2010), but in the retina astrocytes are confined to the SVP, where they, together with radial Müller glia, wrap vessels (Albargothy et al, 2023) (Figure 1, S1). In the IVP and DVP, only Müller glia wrap capillaries, as shown in cat (Hollander et al, 1991), tree shrew (Ochs et al, 2000; Reichenbach et al, 1995), and human (Erskine, 1963).…”

Retinal Ischaemia in Diabetic Retinopathy: Understanding and Overcoming a Therapeutic Challenge

“…There is close talk and cell-to-cell interactions between endothelial cells and pericytes through gaps in the shared basement membrane [ 11 ]. These interactions, recently described as being of two types, direct contact points or pericyte-endothelial peg-and-socket formations [ 12 ], seem to be crucial to maintain a stable endothelium. Muller cells wrap around retinal capillaries; gaps in the basement membrane have been identified, however, which allow contact between Muller cells and pericytes [ 12 ], as well as areas lacking this Muller cell coverage, where neurons meet the vascular basement membrane [ 12 ].…”

“…These interactions, recently described as being of two types, direct contact points or pericyte-endothelial peg-and-socket formations [ 12 ], seem to be crucial to maintain a stable endothelium. Muller cells wrap around retinal capillaries; gaps in the basement membrane have been identified, however, which allow contact between Muller cells and pericytes [ 12 ], as well as areas lacking this Muller cell coverage, where neurons meet the vascular basement membrane [ 12 ]. Given the lack of autonomic innervation in the inner retina, the neurovascular unit and the “dialogue” among its different components are key to controlling blood flow, adjusting it depending on the requirements of the neuropile and maintaining it relatively constant despite changes in arterial and/or intraocular pressure [ 13 , 14 ].…”