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Several evidences suggest that the pro-inflammatory cytokines IL-1b and the radical NO are implicated as effectors molecules in the pancreatic b-cells dysfunction; an event preceding the pathogenesis of diabetes. IL-1b induces the expression of the inducible isoform of NO synthase (iNOS), which use L-arginine as substrate to overproduce NO. However, it is not known whether these events may participate in the development of diabetic retinopathy, which is the main cause of blindness. In this work, we found an increased level of IL-1b in retinas from streptozotocin-induced (STZ) diabetic rats. We also observed that the activity of the NO synthase (NOS) and the L-arginine uptake are enhanced in retinas from STZ-induced diabetic rats as compared to retinas from control rats. We found that the uptake of L-arginine in retinas from control and diabetic rats occurs through a transporter resembling the Y system, i.e. it is saturable, not affected over the pH range 6.5 to 7.4, and is independent of the extracellular Na. Nevertheless, the L-arginine transport in retinas from diabetic rats occurs through a carrier with lower affinity (Km25 mM) and higher capacity (Vmax295922.4 pmol L-arginine:mg protein) than in retinas from control rats (Km 5 mM and Vmax158912.8 pmol L-arginine:mg protein) which is correlated with the increased NOS activity and consequent depletion of the intracellular pool of L-arginine. © 1999 Elsevier Science Ltd. All rights reserved.

A continuous fluorometric assay was adapted to measure the release of endogenous glutamate from cultured chick retinospheroids. The results obtained with this technique are compared with the release of [3H]d-aspartate from monolayer cultures of chick retina cells. It is shown that although excitatory amino acids may be released in a Ca2+-dependent manner, most of the neurotransmitter release from cultured retina cells occurs by reversal of the glutamate transporter. The presence of extracellular Ca2+ may actually inhibit glutamate release by the cells present in the retinospheroids, or the [3H]d-aspartate release by cells in monolayers, when veratridine is the depolarizing agent. Copyright © 1996 Elsevier Science Ltd.

The effect of glutamate receptor agonists on the intracellular free calcium concentration ([Ca2+]i), measured with Indo-1, was studied in populations of cultured chick embryonic retina cells. The agonists of the ionotropic glutamate receptors,N-methyl-d-aspartate (NMDA), kainate, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) increased the [Ca2+]i through a composite effect, comprising Ca2+ permeating the receptor-associated channels, and Ca2+ entering through voltage-gated Ca2+ channels. Furthermore, the [Ca2+i responses to NMDA and AMPA also involved Ca2+ release from intracellular stores, which could not be mobilized by stimulation of the metabotropic receptor.