NEUROCHEMICAL DEVELOPMENT OF THE DEGENERATING RAT RETINA

The Royal College of Surgeons' (RCS) rat is an experimental model for a group of hereditary retinal diseases commonly called retinitis pigme ntosa. We used postembedding immunocytochemistry to determine the loca lisation of glutamate, gamma-aminobutyric acid (GABA), glycine, aspart ate, glutamine, taurine, and arginine in the RCS rat retina during pos tnatal development. In addition, we evaluated the uptake characteristi cs for the three dominant amino acid neurotransmitters, glutamate, GAB A, and glycine. Whereas, cellular localisation of all amino acids was similar to control retinas, there were major changes in the level of i mmunoreactivity, even before eye opening, and well before the onset of visibly detectable photoreceptor degeneration. Two major patterns eme rged. First, neurochemical changes evident before degeneration, involv ing the amino acids glutamate, GABA, aspartate, glutamine, and arginin e. Second, neurochemical changes that become evident during photorecep tor degeneration involving the amino acids taurine and glycine. Anomal ies in uptake characteristics also become evident during the degenerat ion phase and are likely to reflect changes in cellular function as a consequence of the degeneration process. Neurochemical changes evident before photoreceptor degeneration involve both glutamate and GABA man ufacturing pathways. Muller's cells displayed elevated levels of gluta mine and arginine from an early age, and the neuroblastic layer in the RCS retina showed high glutamate levels. Modified aspartate immunorea ctivity began at postnatal day 11 and is consistent with altered metab olic activity. These results suggest that amino acid neurochemistry is different in the RCS rat retina from an early age, which may indicate an underlying metabolic defect affecting multiple cell classes. (C) 1 997 Wiley-Liss, Inc.