Differential expression of glutamate decarboxylase isoforms in the horizontal cells of human and rat retinas

Abstract

L-glutamate decarboxylase (GAD) isoforms, GAD65 and GAD67, catalyze thesynthesis of c-aminobutyric acid (GABA). Previous studies demonstrated thatGAD65 and GAD67 appear only in the horizontal cells of monkey, and rodentsand cats, respectively; whereas both GAD65 and GAD67 can be found in therabbit horizontal cells. In the present study, we used immunohistochemistry andWestern blot to examine the expression of GAD isoforms in the retinas of humanfetuses and also in the developing and adult rat retinas. We found that both GADisoforms existed in the amacrine cells and the inner plexiform layer of both humanand rat retinas. GAD67 was found in the more early stage and more in the cellbodies. Two GAD isoforms were detected in a different stratification pattern of theinner plexiform layer. However, only GAD65 was observed transiently in thehorizontal cells, at 22 WG of human fetus; while both isoforms were found in rats.GAD67 was first seen at birth and GAD65 at postnatal 14 days and through adultin rats. Previous studies provided evidences that GABAc receptor is expressed inthe bipolar cells and cone photoreceptors. Thus GABA released by horizontal cellswas hypothesized to act as a forward feedback to bipolar cells and a backwardfeedback to cone photoreceptors. In summary, GAD isoforms catalyzing GABAsynthesis in the horizontal cells are different among different species and onlyGAD65 plays a role in the horizontal cells of human fetuses.Acknowledgements: Support: The University of Hong Kong, Institute ofMolecular Technology for Drug Discovery and Synthesis of HKU, and ResearchGrant Council of Hong Kong.