SYNTHESIS OF SEROTONIN FROM 5-HYDROXYTRYPTOPHAN IN THE POST-CRUSH RETINA - INHIBITION OF IN-VITRO OUTGROWTH BY THE INTRAOCULAR ADMINISTRATION OF THE PRECURSOR

Serotonin is present in the retina of many species, in which plays rol es as a neurotransmitter, as a modulator of regeneration, and as the p recursor of melatonin. The turnover of serotonin in the goldfish retin a is modified by the lesion of the optic nerve and, in postcrush goldf ish retinal explants, serotonin inhibits the outgrowth. In the present study, the modification of the serotonergic system of the retina indu ced by the process of regeneration was explored. The addition of the p recursor of serotonin, 5-hydroxytryptophan, to retinal explants, incre ased the levels of serotonin in a concentration-dependant manner. The concentration of serotonin differentially increased in control and pos tcrush explants cultured in the presence of 5-hydroxytryptophan for va rious periods of time, indicating a greater accumulation of the indole amine at early periods of time in the control than in the postcrush ti ssue culture. This observation, together with the fact that serotonin concentration in postcrush retina cultured in the absence of 5-hydroxy tryptophan and exposed to the precursor for 60 min increased less than in the control, indicates a saturation of the serotonergic system pro duced by the lesion. The addition of imipramine or citalopram, seroton in uptake blockers, did not significantly change the concentration of serotonin in the cultures, thus, the elevation of serotonin accumulati on, especially in the post-crush tissue, might not be due to the trans port from the medium. The intraocular injection of 5-hydroxytryptophan after the crush of the optic nerve resulted in a decrease in the outg rowth of retinal explants, supporting the in vivo role of serotonin du ring the regenerating process in situ. The lesion of the optic nerve d id not affect the specific cells, since the number of serotonin-immuno reactive neurons in the retina were not modified by the crush. Taken t ogether, retinal serotonin system is regulated after producing a lesio n of the optic nerve, a modulation which has been demonstrated in vivo and in vitro. Thus, there is a reciprocal interaction, since serotoni n influences outgrowth in the postcrush retina and the serotonergic sy stem is modulated by the crush, indicating a mechanism of feed-back re gulation.