PROTECTION OF RETINAL GANGLION-CELLS FROM NATURAL AND AXOTOMY-INDUCEDCELL-DEATH IN NEONATAL TRANSGENIC MICE OVEREXPRESSING BCL-2

Approximately half of the retinal ganglion cells (RGCs) present in the rodent retina at birth normally die during early development. Overexp ression of the proto-oncogene bcl-2 recently has been shown to rescue some neuronal populations from natural cell death and from degeneratio n induced by axotomy of nerves within the peripheral nervous system. H ere we study in vivo the role of the overexpression of bcl-2 in the na tural cell death of RGCs and in the degenerative process induced in th ese cells by transection of the optic nerve. We find that in newborn b cl-2 transgenic mice, the number of RGCs undergoing natural cell death is considerably lower than in wild-type pups. Consistently, a vast ma jority (90%) of the ganglion cells found in the retina of neonatal tra nsgenics are maintained in adulthood, whereas only 40% survive in wild -type mice. After transection of the optic nerve, the number of degene rating ganglion cells, determined by counting pyknotic nuclei or nucle i with fragmented DNA, is substantially reduced in transgenic mice. In wild-type animals, almost 50% of ganglion cells degenerate in the 24 hr after the lesion, whereas almost the entire ganglion cell populatio n survives axotomy in transgenic mice. Therefore, overexpression of bc l-2 is effective in preventing degeneration of this neuronal populatio n, raising the possibility that ganglion cells are dependent on the en dogenous expression of bcl-2 for survival. The remarkable rescue capac ity of bcl-2 overexpression in these neurons makes it an interesting m odel for studying natural cell death and responses to injury in the CN S.