Fragile X Mental Retardation Protein expression in the retina is regulated by light.

Fragile X Mental Retardation Protein (FMRP) is a RNA-binding protein that modulates protein synthesis at the synapse and its function is regulated by glutamate. The retina is the first structure that participates in vision, and uses glutamate to transduce electromagnetic signals from light to electrochemical signals to neurons. FMRP has been previously detected in the retina, but its localization has not been studied yet. In this work, our objectives were to describe the localization of FMRP in the retina, to determine whether different exposure to dark or light stimulus alters FMRP expression in the retina, and to compare the pattern in two different species, the mouse and chick. We found that both FMRP mRNA and protein are expressed in the retina. By immunohistochemistry analysis we found that both mouse and chick present similar FMRP expression localized mainly in both plexiform layers and the inner retina. It was also observed that FMRP is down-regulated by 24 h dark adaptation compared to its expression in the retina of animals that were exposed to light for 1 h after 24 h in the dark. We conclude that FMRP is likely to participate in retinal physiology, since its expression changes with light exposure. In addition, the expression pattern and regulation by light of FMRP seems well conserved since it was similar in both mouse and chick.

Selective activation of group III metabotropic glutamate receptor subtypes produces different patterns of γ-aminobutyric acid immunoreactivity and glutamate release in the retina.

Glutamate, the major excitatory neurotransmitter in the retina, functions by activation of both ionotropic (iGluR) and metabotropic (mGluR) glutamate receptors. Group III mGluRs, except for mGluR6, are mostly found in the inner plexiform layer (IPL), and their retinal functions are not well known. Therefore, we decided to investigate the effect of mGluRIII on glutamate release and GABAergic amacrine cells in the chick retina. The nonselective mGluRIII agonist L-SOP promoted a decrease in the number of γ-aminobutyric acid (GABA)-positive cells and in the GABA immunoreactivity in all sublayers of the IPL. This effect was prevented by the antagonist MAP-4, by GAT-1 inhibitor, and by antagonists of iGluR. Under the conditions used, L-SOP did not alter endogenous glutamate release. VU0155041, an mGluR4-positive allosteric modulator, reduced GABA immunoreactivity in amacrine cells and in sublayers 2 and 4 of the IPL but evoked an increase in the glutamate released. VU0155041's effect was inhibited by the absence of calcium. AMN082, a selective mGluR7-positive allosteric modulator, also decreased GABA immunoreactivity in amacrine cells and sublayers 1, 2, and 3 and increased glutamate release, and this effect was also inhibited by calcium absence. DCPG, an mGluR8-selective agonist, did not significantly alter GABA immunoreactivity in amacrine cells or glutamate release. However, it did significantly increase GABA immunoreactivity in sublayers 4 and 5. The results suggest that mGluRIIIs are involved in the modulation of glutamate and GABA release in the retina, possibly participating in distinct visual pathways: mGluR4 might be involved with cholinergic circuitry, whereas mGluR7 and mGluR8 might participate, respectively, in the OFF and the ON pathways.

A calcium-dependent glutamate release induced by metabotropic glutamate receptors I/II promotes GABA efflux from amacrine cells via a transporter-mediated process.

Glutamate and GABA are, respectively, the major excitatory and inhibitory neurotransmitters in the retina, participating in the two pathways through which the retina processes light information. It has already been shown that glutamate induces GABA release from amacrine cells through a transporter-mediated mechanism, and that this process is mediated by ionotropic glutamate receptors. It is well established that glutamate can also activate metabotropic glutamate receptors, which are widely distributed in the retina, and can be detected in amacrine cell bodies and synaptic contacts. Thus, we decided to investigate the role of the activation of groups I and II metabotropic glutamate receptors in GABA release from amacrine cells in the chicken retina. Group I/II agonist trans-ACPD promoted a 40% decrease in the number of GABA-positive cells in relation to the control, effect that was prevented by antagonists of both groups. Also, the trans-ACPD effect was blocked by GAT-1 inhibitor or by antagonists of ionotropic glutamate receptors. Trans-ACPD induced release of GABA was abolished when the experiment was conducted in absence of calcium ions. Under the superfusing conditions used, trans-ACPD promoted an increase in endogenous glutamate release that was prevented when calcium was omitted from the bathing medium. The results suggest that mGluRI/II regulate the release of glutamate, likely from bipolar cells, that in turn activates GABA release from amacrine cells via a transporter mediated process.

Modulation of GABA release by nitric oxide in the chick retina: different effects of nitric oxide depending on the cell population.

gamma-Aminobutyric acid (GABA) is considered to be the most important inhibitory neurotransmitter in the central nervous system, including the retina. It has been shown that nitric oxide (NO) can influence the physiology of all retinal neuronal types, by mechanisms including modulation of GABA release. However, until now, there have been no data concerning the effects on endogenous GABA release of NO produced by cells in the intact retina. In the present study, we have investigated how NO production induced by drugs influences the release of endogenous GABA in cells of the intact retina of mature chicken. Retinas were exposed to different drugs that affect NO production, and GABA remaining in the tissue was detected by immunohistochemical procedures. A specific nNOS inhibitor (7-NI) reduced the number of GABA+amacrine cells and cells in the ganglion cell layer (GCL) by 33% and 41%, respectively. A GABA transporter inhibitor blocked this effect. L-arginine (100 microM), the precursor of NO, induced increases of 62% and 34% in the number of GABA+amacrine cells and GCL cells, respectively. A sodium (Na(+))-free solution, 7-NI and a PKG inhibitor prevented the effect of L-arginine (100 microM). However, a higher concentration of L-arginine (1mM) induced a 35% reduction in the number of GABA+cells by a Na(+)-dependent mechanism that was restricted to the GCL population. NMDA, which stimulates NO production, increased GABA release as indicated by 53% and 38% reductions in the number of GABA+amacrine cells and GCL cells, respectively. This effect was blocked by 7-NI only in GCL cells. We conclude that basal NO production and moderate NO production (possibly induced by L-arginine; 100 microM) inhibit basal GABA release from amacrine cells and GCL cells. However, NMDA or L-arginine (1mM) induce a NO-dependent increase in GABA release in GCL cells, possibly by stimulating higher NO production.