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 pigmentosa. We used postembedding immunocytochemistry to determine the localisation of glutamate, gamma-aminobutyric acid (GABA), glycine, aspartate, glutamine, taurine, and arginine in the RCS rat retina during postnatal development. In addition, we evaluated the uptake characteristics for the three dominant amino acid neurotransmitters, glutamate, GABA, and glycine. Whereas, cellular localisation of all amino acids was similar to control retinas, there were major changes in the level of immunoreactivity, even before eye opening, and well before the onset of visibly detectable photoreceptor degeneration. Two major patterns emerged. First, neurochemical changes evident before degeneration, involving the amino acids glutamate, GABA, aspartate, glutamine, and arginine. Second, neurochemical changes that become evident during photoreceptor degeneration involving the amino acids taurine and glycine. Anomalies in uptake characteristics also become evident during the degeneration 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 manufacturing pathways. Müller's cells displayed elevated levels of glutamine and arginine from an early age, and the neuroblastic layer in the RCS retina showed high glutamate levels. Modified aspartate immunoreactivity began at postnatal day 11 and is consistent with altered metabolic 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.
Fletcher
E L
EL
Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Australia.
Kalloniatis
M
M
D000375:Aging / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007150:Immunohistochemistry; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011915:Rats, Inbred BUF; D011922:Rats, Mutant Strains; D012160:Retina / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013654:Taurine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D005973:Glutamine; D013654:Taurine; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D001120:Arginine; D005998:Glycine