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Their opposing apical surfaces delineate the subretinal space, a specialized extracellular compartment housing the light\u2010detecting outer segments of photoreceptors. Although the individual interactions between these supporting cells and photoreceptors have been extensively characterized, M\u00fcller 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\u2010SEM and confocal microscopy imaging of the zebrafish and mouse outer retina. We demonstrate that both M\u00fcller 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 M\u00fcller 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\u2013RPE interactions are enriched at cone\u2010associated 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 M\u00fcller glia, RPE, and photoreceptors that is conserved across vertebrate species.<\/jats:p>","DOI":"10.1002\/glia.70241","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:06:49Z","timestamp":1792602409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A M\u00fcller Glia\u2010Retinal Pigment Epithelium Apical Network Surrounding Cone Outer Segments in Fish and Mouse"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4980-4811","authenticated-orcid":false,"given":"Maria","family":"Sharkova","sequence":"first","affiliation":[{"name":"Division of Anatomy, Department of Surgery, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Department 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Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Amidian","sequence":"additional","affiliation":[{"name":"Cell Imaging Core, B\u2010120 Katz Group Centre, Faculty of Medicine and Dentistry, University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-9048","authenticated-orcid":false,"given":"Michel","family":"Cayouette","sequence":"additional","affiliation":[{"name":"Cellular Neurobiology Research Unit Institut de Recherches Cliniques de Montr\u00e9al (IRCM)  Montreal Quebec Canada"},{"name":"Integrated Program in Neuroscience, McGill University  Montreal Quebec Canada"},{"name":"Department of Anatomy and Cell Biology McGill University  Montreal Quebec Canada"},{"name":"Department of Medicine Universit\u00e9 de Montr\u00e9al  Montreal Quebec 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