Myelination of the rat retina by transplantation of oligodendrocytes into 4-day-old hosts

Oligodendrocyte transplantation into the retina enables us to investigate the early events in myelin formation in a new in vivo system. The axons of rat retinal ganglion cells are unmyelinated in the eye but should express a myelination initiation signal since they acquire myelin posterior to the globe. The lamina cribrosa may block the migration of oligodendrocytes from the optic nerve into the retina. Animals that lack a lamina cribosa such as the rabbit have myelinated retinas. We have bypassed the lamina cribrosa by using transplantation techniques and inserted freshly isolated syngeneic 3-week-old rat oligodendrocytes into the unmyelinated 4-day-old rat retina during the period of active optic nerve myelination. The animals are sacrificed at 1-week intervals for 8 weeks. The retinas are examined immunocytochemically for myelin with an antibody to myelin basic protein (MBP). MBP-positive cells are seen extending processes at 1 and 2 weeks. Three and four week retinas show the formation of thicker and longer myelin sheaths oriented along the same radial path as the retinal ganglion axons with maximal MBP staining intensity seen by 5 weeks. Transplanted retinas are negative when stained for Po, a Schwann cell antigen, ruling out Schwann cell myelination of our retinas. We have shown that rat cerebral oligodendrocytes survive, mature, and express a myelin-specific protein in the retinal environment in a pattern consistent with myelination of ganglion cell axons. Retinal transplantation provides a new in vivo model to study oligodendrocyte development and axonal-glial interactions, free from the difficulties inherent in culture systems.