Axonal Tracing of the Normal and Regenerating Visual Pathway of Mouse, Rat, Frog, and Fish Using Manganese-Enhanced MRI (MEMRI)

Purpose: To assess optic nerve (ON) regeneration after injury by applying manganese-enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species. Materials and Methods: The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl2 injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONC+PNG; rats) or lens injury (ONC+LI; mice) and monitored by MEMRI at 1 and 20 days post-lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl). Results: Signal intensity profiles of the Mn2+-enhanced ON were consistent with ON regeneration in the ONC+PNG and ONC+LI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn2+-enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration. Conclusion: Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species.