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Peer-reviewedCC BY-NC-NDGlia

A Müller Glia-Retinal Pigment Epithelium Apical Network Surrounding Cone Outer Segments in Fish and Mouse.

9 affiliations
  1. 1Division of Anatomy, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
  2. 2Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
  3. 3Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
  4. 4Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.
  5. 5Cell Imaging Core, B-120 Katz Group Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
  6. 6Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
  7. 7Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
  8. 8Women and Children's Health Research Institute, 5-083 Edmonton Clinic Health Academy, University of Alberta, Edmonton, Alberta, Canada.
  9. 9Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Abstract

Homeostasis of the vertebrate retina critically depends on two non-neuronal cell populations, Müller glia and the retinal pigment epithelium (RPE). Their opposing apical surfaces delineate the subretinal space, a specialized extracellular compartment housing the light-detecting outer segments of photoreceptors. Although the individual interactions between these supporting cells and photoreceptors have been extensively characterized, Müller glia and the RPE have long been presumed to remain physically separate in the healthy retina. Here, we challenge this assumption and present a revised model of the subretinal space architecture based on detailed FIB-SEM and confocal microscopy imaging of the zebrafish and mouse outer retina. We demonstrate that both Müller glia and the RPE extend long apical processes that not only contact one another but also collectively ensheath cone outer segments, forming a previously unrecognized tripartite interface. These contact regions are highly elaborated in fish and, while comparatively sparser, are still present in mouse. Developmentally, the growth and interdigitation of Müller glial and RPE apical processes follow the emergence of the outer segment in both species and, in mouse, coincides with the onset of visual function. Although glial-RPE interactions are enriched at cone-associated sites, their presence is not strictly dependent on cone localization in either species, suggesting they represent a fundamental feature of the vertebrate subretinal space. Together, these findings revise our understanding of the subretinal space cytoarchitecture and reveal a previously unappreciated structural interaction between Müller glia, RPE, and photoreceptors that is conserved across vertebrate species.

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BibTeX
@article{sharkova2026müller,
  title = {{A Müller Glia-Retinal Pigment Epithelium Apical Network Surrounding Cone Outer Segments in Fish and Mouse.}},
  author = {Maria Sharkova and Michael Housset and Samantha Boudreau and Chavy Dworkind and Sara Amidian and Michel Cayouette and Jennifer C Hocking},
  journal = {Glia},
  year = {2026},
  month = oct,
  doi = {10.1002/glia.70241},
  url = {https://europepmc.org/article/MED/42905611},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - A Müller Glia-Retinal Pigment Epithelium Apical Network Surrounding Cone Outer Segments in Fish and Mouse.
AU  - Maria Sharkova
AU  - Michael Housset
AU  - Samantha Boudreau
AU  - Chavy Dworkind
AU  - Sara Amidian
AU  - Michel Cayouette
AU  - Jennifer C Hocking
PY  - 2026
DA  - 2026/10/30
JO  - Glia
DO  - 10.1002/glia.70241
UR  - https://europepmc.org/article/MED/42905611
AB  - Homeostasis of the vertebrate retina critically depends on two non-neuronal cell populations, Müller glia and the retinal pigment epithelium (RPE). Their opposing apical surfaces delineate the subretinal space, a specialized extracellular compartment housing the light-detecting outer segments of photoreceptors. Although the individual interactions between these supporting cells and photoreceptors have been extensively characterized, Müller glia and the RPE have long been presumed to remain physically separate in the healthy retina. Here, we challenge this assumption and present a revised model of the subretinal space architecture based on detailed FIB-SEM and confocal microscopy imaging of the zebrafish and mouse outer retina. We demonstrate that both Müller glia and the RPE extend long apical processes that not only contact one another but also collectively ensheath cone outer segments, forming a previously unrecognized tripartite interface. These contact regions are highly elaborated in fish and, while comparatively sparser, are still present in mouse. Developmentally, the growth and interdigitation of Müller glial and RPE apical processes follow the emergence of the outer segment in both species and, in mouse, coincides with the onset of visual function. Although glial-RPE interactions are enriched at cone-associated sites, their presence is not strictly dependent on cone localization in either species, suggesting they represent a fundamental feature of the vertebrate subretinal space. Together, these findings revise our understanding of the subretinal space cytoarchitecture and reveal a previously unappreciated structural interaction between Müller glia, RPE, and photoreceptors that is conserved across vertebrate species.
SN  - 0894-1491
SN  - 1098-1136
ER  -