Penetration of horseradish peroxidase into the optic nerve after vitreal or vascular injections in the developing chick.

In order to determine whether a possible barrier exists to diffusion of tracer into the optic nerve during development and to provide a basis for later studies of retrograde axonal transport in embryonic nerves, we studied the diffusion of horseradish peroxidase (HRP) into the nerve after vitreal injections in chicks ranging in age from embryonic day 6 to 3 days after hatching. We found that HRP may reach the periaxonal spaces of the retrobulbar optic nerve after vitreal injection, vitreal injection into the opposite eye, or vascular injection. These and other observations suggest that vitreally injected HRP may reach the periaxonal spaces of the optic nerve by at least two routes: (1) by the obvious diffusion of marker from the vitreal surface into the optic nerve head and (2) by vascular leakage from fenestrated capillaries of the choriocapillaris into the pericapillary spaces of these and other capillaries that feed into the optic nerve parenchyma. There is a breakdown in the blood-brain barrier to HRP in the optic nerve head of the chick at embryonic day 13. The development of the breakdown depends at least in part on the maturation of vasculature in the nerve and the establishment of anastomotic branches between these vessels and those of the choriocapillaris. Our results further suggest that the limited diffusion of HRP into the retrobulbar nerve of fetal and newly hatched chicks is a function of uptake of tracer by glial cells within the nerve. Investigators of axonal transport who use this visual pathway as a model should be reminded of the potential artifact involved in this access of vascularly circulating label into the region of the lamina cribrosa.