Substance P acid vasoactive intestinal polypeptide in the streptozotocin-induced diabetic rat retina

PURPOSE. Little knowledge exists about how neurotransmitters behave in the diabetic retina. In this study. the authors measured the concentration of t wo neuropeptides, substance P and vasoactive intestinal polypeptide, in the streptozotocin-induced diabetic rat retina in a time-dependent manner. METHODS. The retinas of 1-, 3-, 5-, 8-, and 12-week diabetic rats were proc essed using a highly sensitive radioimmunoassay for both substance P and va soactive intestinal polypeptide. Furthermore, the peptide-immunoreactivitie s were characterized by high-pressure liquid chromatography. RESULTS. Substance P and vasoactive intestinal polypeptide were found to be significantly reduced with a maximum decrease of 28.6% (+/-6.7) and 64.5% (+/- 10.7) after 5 weeks, respectively. The peptide-immunoreactivities were found in a major peak coeluting with the synthetic peptides indicating tha t the quantitative values measured by radioimmunoassay represent the authen tic peptides. CONCLUSIONS. The reduction of substance P and vasoactive intestinal polypep tide is in clear contrast to the amino acid transmitters GABA and glycine. which have been shown to be elevated in this early stage of diabetic retino pathy. This finding is important for three reasons: First, the decrease may result in reduced excitability of inner retinal neurons, as both peptides are known to modulate the excitability of these neurons; sec end, the decre ase may be the consequence of a depressing and/or damaging effect by excito toxins; and third. it may help explain why neovascularizations do not occur in this animal model, although VEGF is massively upregulated, as substance P is a very potent vascular growth factor.