A Multidisciplinary Approach to Investigating Optic Nerve Regeneration in the Goldfish

Abstract

Unlike the mammalian central nervous system, the goldfish optic nerve can regenerate after transection. We have used this regenerative ability to examine possible factors involved in this process. By monitoring goldfish behavior, we found two phases of recovery. Simple behavioral patterns such as tilting and turning return one month after optic nerve transection (fast recovery phase), whereas more complex behaviors such as schooling behavior require up to 4 months or more to recover (slow recovery phase). We also demonstrated that severe hypertrophy occurs in retinal ganglion cells after optic nerve transection, taking about 4 months to recover. Our most recent investigations have looked at various aspects of the fast recovery phase using histochemical and molecular techniques. We have observed that there is an increase in the amount of the nitric oxide (NO) synthesizing enzyme (NOS) in retinal ganglion cells during the first month after optic nerve section. During optic nerve regeneration NO may play a role in strengthening regenerating connections between the retina and tectum. Finally, we have investigated changes in gene expression in the retina during optic nerve regeneration. Of the molecules that we have studied, transglutaminase (TG) and Na-K ATPase appear to be the most interesting. There is an increase in tissue TG gene expression in the retina at about one week after optic nerve section. Na-K ATPase alpha-3 subunit activity in the retina also peaked around this time. Using this multidisciplinary approach, we hope to gain a better understanding of many aspects of regeneration, from genetic control to behavioral modification.