Neurotoxic effects of L-alpha-aminoadipic acid on the carp retina: a long term observation

The hypothesis has been tested that the enantiomers of alpha-aminoadipic acid have different target effects; the L-isomer has both glio- and neurotoxic actions, while the DL-isomer has a gliospecific action in the CNS. Electrophysiological and morphological studies were carried out on the retina of the carp (Cyprinus carpio) for one to two months after intraocular injection with alpha-aminoadipic acids at various doses. Intracellular recording from horizontal cells and extracellular recording of spike discharges from ganglion cells in isolated retinal preparations were made from control and pretreated retinas at various intervals after intraocular injection with the enantiomers. In control retinas, application of 15 mM L-alpha-aminoadipic acid in the superfusate resulted in hyperpolarization of all horizontal cells and in a decrease in amplitude of their light responses (S-potentials). In the retinas pretreated with L-alpha-aminoadipic acid (8 mumol), low amplitude S-potentials were seen during an early phase 2-4 h after ocular injection, but the normal appearance of S-potentials was restored one day after injection. In control retinas, a brief period of iontophoretic application of L-alpha-aminoadipic acid resulted in a slight activation of the spontaneous spike firing of ganglion cells but a slight decrease in the rate of light-induced firing. In retinas pretreated with intraocular L-alpha-aminoadipic acid (4 mumol) 4 h prior to eye removal, however, light-induced spike discharges were abolished from nearly all spontaneously firing ganglion cells (greater than 90%). Their unresponsiveness to light stimuli lasted for more than two months after injection, and was accompanied by insensitivity to iontophoretically applied putative neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS)