Summary: Dr. Goldberg's laboratory is investigating the developmental control of axon growth by retinal ganglion cells and other CNS neurons, and on understanding why retinal ganglion cells fail to survive and regenerate after injury. We use a combination of cellular and molecular approaches to address these questions.

Jeffrey L. Goldberg, M.D., Ph.D.
Assistant Professor of Ophthalmology

View published research articles by this doctor in the National Library of Medicine.

Current Projects

The signals required to induce rapid regeneration in vivo. Survival and axon regeneration have have been difficult to study independently in neurons. In vitro and in vivo, peptide factors that induce survival similarly induce axon growth. Withdrawing or blocking such factors to study whether they are necessary for axon growth leads to neuronal death, confounding the experiment. We have been able to circumvent this problem by ensuring retinal ganglion cell (RGC) survival by manipulating the levels of the apoptotic protein machinery. We are then free to add signaling molecules or stimulate RGCs with electrical activity and ask, what signals induce axon growth? Current aims include investigating the mechanism by which electrical activity induces increased responsiveness to trophic signaling in RGCs.

The cellular basis for the developmental loss of axon growth ability. Using strongly growth-promoting culture conditions, we found that embryonic RGCs extended axons at about 0.5mm/day, about the rate they grow in vivo, but that postnatal or adult RGCs grew about 10 times more slowly. RGCs must be signaled in vivo to decrease this intrinsic growth ability, because purified embryonic RGCs do not show a similar maturation in vitro. Retinal amacrine cells, but not target cells from the superior colliculus, were sufficient to signal E20 RGCs to decrease their growth ability. Neither retinal, optic nerve, or superior collicular cells, nor Schwann cells, were able to signal the postnatal RGCs to revert to a faster, embryonic growth rate. Concurrent with this decrease in axon growth ability, RGCs increased their dendrite growth ability. This increase was likewise signaled by a retinal cue. Currently we are investigating whether this retinal cue is similarly signaled by amacrine cells, and whether the loss of axon growth ability represents a true switch to dendrite growth ability, or these are two separate but concurrent phenomena.

The molecular basis for the switch from axonal to dendritic growth. Thus retinal neurons signal RGCs to undergo an apparently irreversible switch from axon to dendrite growth ability. We are comparing the transcriptome of RGCs through development to identify molecular candidates that may underlie the developmental loss of axon growth ability. We have optimized gene transfection into purified RGCs and will test these gene candidates in vitro and in vivo.

Retinal ganglion cells extending axons over the surface of a silicon chip used to electrically stimulate the neurons.