The Role of GABA During Development of the Outer Retina in the Rabbit

Horizontal cells are among the first to mature in the neonatal mammalian retina and they are the first to establish the position of the outer synaptic layer which is subsequently formed by invading terminals of both rod and cone photoreceptors. During the period of cone synaptogenesis, horizontal cells transiently express the full complement of GABAergic properties (uptake, release, synthesis and storage of GABA); later during development of rod terminals, these properties are down-regulated. Given the reports of GABA's role in other developing neuronal systems (for review: 10), we have examined the effect that GABA, produced from horizontal cells, might have on photoreceptor maturation in rabbit retina. Results from our previous studies show that lesioning the horizontal cell with kainic acid in vivo leads to a displacement of cone photoreceptor cells and a disappearance of their synaptic terminals, while rod cells maintain their normal position and produce an overabundance of terminals. Similar effects are seen with the GABA-A receptor antagonists, picrotoxin and bicuculline. New evidence from 3H-thymidine studies suggests that the effects of kainic acid are specific and that cell division, migration and differentiation in other cell types do not appear to be affected. This body of work is summarized and possible mechanisms of action are suggested which could account for the apparent ability of GABA to help maintain the normal position of cone cell bodies and regulate cone synaptogenesis.