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

Müller 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 Müller 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 Müller glia in vertebrate retinas: a modified enzyme lectin (GFP-EndoN DM ) 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 Müller glia predominantly in the form of polySia-NCAM. We used GFP-EndoN DM and mAb735 to investigate polySia distribution in Müller glia of fish, amphibians, reptiles, birds, rodents, retinal organoids, and humans. In adult retinas of most species, polySia was localized to the Müller 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 Müller glia were labelled in adult zebrafish, whereas the outer Müller 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 Müller glia markers, and offers a versatile way to visualize and monitor structural changes in non-reactive and reactive Müller glia across most vertebrate species.