Co-localization of glutamate and homocysteic acid immunoreactivities in human photoreceptor terminals.

Consecutive semithin sections of human retinae were treated with antisera recognizing fixed homocysteic acid, glutamate or glutamine. Photoreceptor terminals displayed a co-localization of glutamate-like and homocysteic acid-like immunoreactivities. This was confirmed in the electron microscope by immunogold cytochemistry. A quantitative analysis of the immunogold labelling indicated that glutamate and homocysteic acid occurred at higher concentrations in the terminals than in outer parts of the receptor cells. No such gradient was found for glutamine immunoreactivity, which was concentrated in Müller cell processes. These processes were also labelled by the homocysteic acid antiserum, although less intensely than were the photoreceptor terminals. Control experiments suggested that the homocysteic acid antiserum visualized a pool of authentic homocysteic acid, although it could not be excluded that part of this pool had been generated by non-enzymatic oxidation of precursor molecules. Homocysteic acid immunoreactivity was also demonstrated in photoreceptor terminals of baboon. The present data indicate that primate photoreceptor terminals contain homocysteic acid in addition to glutamate and open up the possibility that homocysteic acid is released as a glutamate co-agonist at photoreceptor synapses.