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September 6th, 2025
Version: 2
The University of Alberta
cell biology
bioRxiv

Polysialic acid is a versatile marker for retinal Müller glia in common vertebrate model organisms and systems

San Juan, A. N.Open in Google Scholar•Tran, A. D. N. N.Open in Google Scholar•Kriese, L. M.Open in Google Scholar•Van Engelen, N. H. N.Open in Google Scholar•Hore, D.Open in Google Scholar•Sharkova, M.Open in Google Scholar•Noel, N. C. L.Open in Google Scholar•Hunter, C.Open in Google Scholar•Spencer Carreira, O.Open in Google Scholar•MacDonald, R. B.Open in Google Scholaret al.

Muller glia are retinal support cells that play crucial roles in tissue structure, waste management, and repair. A challenge for the field has been to find Muller glia markers that detect non-reactive cells or work well in non-mammalian models. We introduce two novel markers for identifying reactive and non-reactive Muller glia in vertebrate retinas: a modified enzyme lectin (GFP-EndoNDM) and a monoclonal antibody (mAb735). These markers recognize polysialic acid (polySia), which is a highly conserved glycosylation modification in humans and vertebrates. In the retina, polySia is present on Muller glia predominantly in the form of polySia-NCAM. We used GFP-EndoNDM and mAb735 to investigate polySia distribution in Muller glia of fish, amphibians, reptiles, birds, rodents, retinal organoids, and humans. In adult retinas of most species, polySia was localized to the Muller glia and spanned outer to inner retina, with inner plexiform layer (IPL) sublaminae ramifications. Gliosis was also detectable in degenerating murine retinas. Notable species differences were that only outer retinal regions of Muller glia were labelled in adult zebrafish, whereas the outer Muller glia body up to the first IPL sublamina was labelled in adult turquoise killifish. There was no significant retinal polySia labeling in larval zebrafish, but it was present in the brain. Larval turquoise killifish have polySia throughout the retina, similar to other adult vertebrates. Labelling polySia expands the scientific toolbox for Muller glia markers, and offers a versatile way to visualize and monitor structural changes in non-reactive and reactive Muller glia across most vertebrate species.

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