Trophic effect of collicular proteoglycan on neonatal rat retinal ganglion cells in situ

Naturally occurring neuronal death is widespread in the central nervous system of mammals. To date, the causes and mechanisms of such death are poorly understood. A major hypothesis is that developing neurons compete for limited amounts of trophic factor(s) released from their target centres as in the case of the peripheral nervous system and nerve growth factor. The present study aims to test this 'trophic hypothesis' in the mammalian central nervous system. In the rat, more than 50% of retinal ganglion cells die in the early post-natal period. Schulz and coworkers [57] purified a potential trophic agent from their major target, the superior colliculus, which was identified as a 480 kDa chondroitin sulfate proteoglycan. This proteoglycan or control solutions were injected into the eyes of rat pups during the post-natal part of the period of naturally occurring ganglion cell death. It was found that the collicular proteoglycan prevented the death of a significant number of the ganglion cells that would normally have been lost over a post-injection period of one or two days. The effect of the proteoglycan was dose- and time-dependent. These results support the notion that trophic interactions are a determining factor in the survival of retinal ganglion cells during the period of naturally occurring cell death. It is also the first time that a proteoglycan has been shown to possess neurotrophic properties in situ.