The Distribution Of BMP-4 In Rat Retina And Optic Nerve And Its Effects On The Differentiation Of Oligodendrocyte Precursors

Duing visual system development, oligodendrocyte precursors originated from brain together in optic chiasm and migrate along the optic nerve towards the retina before differentiating into oligodendrocytes and myelinating the axons of the retinal ganglion cells from late embryonic to early postnatal periods. However, in many mammalian species, myelination of the retinal ganglion cell axons stops at the lamina cribrosa. To explain the pattern of myelination in the optic system of many mammals, a specialized region existed in lamina cribrosa which blocks the migration into the retina of oligodendrocyte precursors is generally related. But its mechanism needs further investigation.Objective By researching the expression of BMP-4 in optic nerve and retina, the effects of BMP-4 to the differentiation of oligodendrocyte precursors and the interrelaionship between BMP-4 and Olig2, we would provide experimental evidences to the lack of myelin in retina and optic nerve head and new ideas to therapy of related myelin diseases.Methods To define in more detail the spatial and temporal distribution of BMP-4 in retina and optic nerve, frozen sections of optic nerve and retina where labeled with antibodies to BMP-4.Using the modified mixed glial culture and different-attachment method, we harvested oligodendrocyte precursors and researched the the induction of BMP-4 to the differentiation of oligodendrocyte precursors. we also researched the relationship between BMP-4 and Olig2 by western blot.Results Strong expression of BMP-4 was detected in the region of the optic nervehead. The cultured oligodendrocyte precursors automatically differentiated into mature oligodendrocytes after PDGF and bFGF withdrawn. Exposed to high concentration of BMP-4 could promote the differentiation of type 2 astrocytes. With the gradually increased concentration of BMP-4, the expression of Olig2 decreased.Conclusion The expression of BMP-4 in the optic nerve head inhibit the differentiation into oligodendrocytes of oligodendrocyte precursors that succeed in migrating through the lamina cribrosa at the optic nerve/retina junction thereby ensuring a lack of retinal myelination. In vitro experiment, BMP-4 suppress oligodendrocyte precursors differentiation into oligodendrocyte and promote the astroglial differentiation.And this effect could be completed by activating some related signal pathway and downregulating the expression olig2.