Purpose: Glycoprotein m6a (M6a) is a cell-surface glycoprotein that belongs to the myelin proteolipid protein family. M6a is expressed mainly in the nervous system, and its expression and function in mammalian retina have not been described. Using proteomics analysis of mouse retinal membrane fractions, we identified M6a as a retinal membrane protein that is strongly expressed at embryonic stages. Our aim was to reveal the function of M6a in development of mouse retina in this work.
Methods: Detailed expression pattern of M6a was examined by immunostaining using frozen sections of mouse retina obtained at various developmental stages. For functional analysis of M6a in mouse retinal development, we performed retorovirus-mediated overexpression of M6a in mouse retinal explant culture. Then, cell differentiation, proliferation and structural maturation of the cells were examined.
Results: M6a transcripts were strongly expressed in embryonic retina. After completion of retinal differentiation, the level of expression decreased as mouse development progressed. Immunohistochemistry showed that in the immature mouse retina, M6a was strongly expressed in the axons of retinal ganglion cells. After birth, M6a expression was confined to the inner plexiform layer, and finally, to the inner and outer plexiform layers of adult mouse retina. M6a expression was completely paralleled by that of the synaptic marker, synaptophysin. Mouse retinal progenitor cells that overexpressed M6a following retrovirus-mediated gene transfer were subjected to in vitro explant or monolayer cultures. The neurite outgrowth of M6a-overexpressing retinal cells was strikingly enhanced, although M6a did not affect differentiation and proliferation.
Conclusions: These results suggest that M6a plays a role in retinal development by regulating neurites, and it may also function to modulate synaptic activities in the adult retina.