Anatomy and spatial organization of Müller glia in mouse retina

Abstract

Müller glia, the most abundant glia of vertebrate retina, have an elaborate morphology characterized by a vertical stalk that spans the retina and branches in each retinal layer. Müller glia play diverse, critical roles in retinal homeostasis, which are presumably enabled by their complex anatomy. However, much remains unknown, particularly in mouse, about the anatomical arrangement of Müller cells and their arbors, and how these features arise in development. Here we use membrane‐targeted fluorescent proteins to reveal the fine structure of mouse Müller arbors. We find sublayer‐specific arbor specializations within the inner plexiform layer (IPL) that occur consistently at defined laminar locations. We then characterize Müller glia spatial patterning, revealing how individual cells collaborate to form a pan‐retinal network. Müller cells, unlike neurons, are spread across the retina with homogenous density, and their arbor sizes change little with eccentricity. Using Brainbow methods to label neighboring cells in different colors, we find that Müller glia tile retinal space with minimal overlap. The shape of their arbors is irregular but nonrandom, suggesting that local interactions between neighboring cells determine their territories. Finally, we identify a developmental window at postnatal Days 6 to 9 when Müller arbors first colonize the synaptic layers beginning in stereotyped inner plexiform layer sublaminae. Together, our study defines the anatomical arrangement of mouse Müller glia and their network in the radial and tangential planes of the retina, in development and adulthood. The local precision of Müller glia organization suggests that their morphology is sculpted by specific cell to cell interactions with neurons and each other.

Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility

“…By eye opening, after P12, processes arborized throughout the IPL and began to resemble their adult distribution, characterized by fewer processes in IPL sublayers S2/S4 than in S1/S3/S5. These observations are consistent with previous findings using the same mouse line and immunohistochemistry in fixed tissue 14 .…”

“…Here we use the mouse retina as a model to explore mechanisms and a possible function of neuron-glia signaling during development. In the retina, Müller glia are the predominant glial type, tiling the entire retinal space and interacting with every retinal cell type 14 . Similar to Bergmann glia of the cerebellum 15,16 , Müller glia exhibit a radial structure with a stalk extending from the soma, lateral processes extending from the stalk within synaptic layers, and endfeet contacting neuronal somata, axons, and vasculature.…”

“…One potential role for wave-associated calcium-signaling in Müller glia is in modulating outgrowth of lateral processes, which initiates and progresses during the same developmental window as retinal waves 14 . In other brain regions and model systems, neuronal activity-evoked calcium transients lead to morphological changes in glial processes.…”

A cell atlas of the chick retina based on single-cell transcriptomics

“…To date, only a single Müller glial type has been identified in mice and primates using scRNAseq ( Macosko et al, 2015 ; Shekhar et al, 2016 ; Peng et al, 2019 ; Yan et al, 2020b ; Wang et al, 2017 ). In contrast, unsupervised analysis of chick Müller glia generated five clusters, which were, however, less well separated from each other than types in other classes.…”

Of neurons and pericytes: The neuro-vascular approach to diabetic retinopathy

“…pigment epithelium (Wang et al, 2017). Following synaptic receptor activation, extracellular glutamate is shuttled inside Müller cells (Barbour et al, 1988;Bringmann et al, 2013) via the glutamate aspartate transporter (GLAST), before conversion to glutamine by the enzyme glutamine synthetase (GS).…”