PubMed ID: 39689705
Author(s): Grimes WN, Berson DM, Sabnis A, Hoon M, Sinha R, Tian H, Diamond JS. Layer-specific anatomical and physiological features of the retina’s neurovascular unit. Curr Biol. 2025 Jan 6;35(1):109-120.e4. doi: 10.1016/j.cub.2024.11.023. Epub 2024 Dec 16. PMID 39689705
Journal: Current Biology : Cb, Volume 35, Issue 1, Jan 2025
The neurovascular unit (NVU), comprising vascular, glial, and neural elements, supports the energetic demands of neural computation, but this aspect of the retina’s trilaminar vessel network is poorly understood. Only the innermost vessel layer-the superficial vascular plexus (SVP)-is associated with astrocytes, like brain capillaries, whereas radial Müller glia interact with vessels in the other layers. Using serial electron microscopic reconstructions from mouse and primate retina, we find that Müller processes cover capillaries in a tessellating pattern, mirroring the wrapping of brain capillaries by tiled astrocytic endfeet. Gaps in the Müller sheath, found mainly in the intermediate vascular plexus (IVP), permit diverse neuron types to contact pericytes and the endothelial cells directly. Pericyte somata are a favored target, often at spine-like structures with reduced or absent vascular basement lamina. Focal application of ATP to the vitreal surface evoked Ca2+ signals in Müller sheaths in all three vascular layers. Pharmacological experiments confirmed that Müller sheaths express purinergic receptors that, when activated, trigger intracellular Ca2+ signals that are amplified by inositol triphosphate (IP3)-controlled intracellular Ca2+ stores. When rod photoreceptors die in a mouse model of retinitis pigmentosa (rd10), Müller sheaths dissociate from the deep vascular plexus (DVP) but are largely unchanged within the IVP or SVP. Thus, Müller glia interact with retinal vessels in a laminar, compartmentalized manner: glial sheaths are virtually complete in the SVP but fenestrated in the IVP, permitting direct neurovascular contacts. In the DVP, the glial sheath is only modestly fenestrated and is vulnerable to photoreceptor degeneration.
Published by Elsevier Inc.