Nitric oxide signaling in the retina: What have we learned in two decades?

Vielma, Alex H.; Retamal, Mauricio A.; Schmachtenberg, Oliver

doi:10.1016/j.brainres.2011.10.045

Cited by 71 publications

(65 citation statements)

References 153 publications

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“…Additionally, NO was observed in many somata in the inner nuclear layer and buttons in the inner plexiform layer in the retina under steady light [36]. However, it has been reported that NADPH-d activity, but not nNOS immunoreactivity, is present in photoreceptor ellipsoids [7], whereas Neufeld et al demonstrated nNOS immunoreactivity in photoreceptors [8]; this discrepancy continues to date [37]. …”

Section: Discussionmentioning

confidence: 97%

Nitrosative Stress in the Rat Retina at the Onset of Streptozotocin-Induced Diabetes

Hernández-Ramírez

Sánchez‐Chávez

Estrella-Salazar

et al. 2017

Cell Physiol Biochem

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Background/Aims. Nitric oxide is a multifunctional molecule that can modify proteins via nitrosylation; it can also initiate signaling cascades through the activation of soluble guanylate cyclase. Diabetic retinopathy is the leading cause of blindness, but its pathogenesis is unknown. Multiple mechanisms including oxidative-nitrosative stress have been implicated. Our main goal was to find significant changes in nitric oxide (NO) levels and determine their association with nitrosative stress in the rat retina at the onset of diabetes. Methods: Diabetes was induced by a single intraperitoneal administration of streptozotocin. The possible nitric oxide effects on the rat retina were evaluated by the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a specific marker for NO-producing neurons, detected by histochemistry performed on whole retinas and retina sections. Immunohistochemistry was also performed on retina sections for iNOS, 3-nitrotyrosine (3-NT) and glial fibrillary acidic protein (GFAP). Retinal nitric oxide levels were assessed by measuring total nitrate/nitrite concentrations. Retinal cGMP levels were determined by radioimmunoassay. Western blots for nitrotyrosine (3-NT) and oxidized proteins were performed. Results: In the present study, we found increased activity of NADPH-diaphorase and iNOS immunoreactivity in the rat retina at the onset of diabetes; this increase correlated with a remarkable increase in NO levels as early as 7 days after the onset of diabetes. However, cGMP levels were not modified by diabetes, suggesting that NO did not activate its signaling cascade. Even so, Western blots revealed a progressive increase in nitrated proteins at 7 days after diabetes induction. Likewise, positive nitrotyrosine immunolabeling was observed in the photoreceptor layer, ganglion cell layer, inner nuclear layer and some Müller cell processes in the retinas of diabetic rats. In addition, levels of oxidized proteins were increased in the retina early after diabetes induction; these levels were reduced by the administration of L-NAME. In addition, stress in Müller cells was determined by immunoreactivity to the glial fibrillary acidic protein. Conclusions: Our findings indicated the occurrence of nitrosative stress at the onset of diabetes in the rat retina and emphasized the role of NO in retinal function and the pathogenesis of retinopathy.

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Section: Discussionmentioning

confidence: 97%

Nitrosative Stress in the Rat Retina at the Onset of Streptozotocin-Induced Diabetes

Hernández-Ramírez

Sánchez‐Chávez

Estrella-Salazar

et al. 2017

Cell Physiol Biochem

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“…The activation of dopamine receptors increases the activity of adenylate cyclase and the cytosolic concentration of cAMP, producing the activation of protein kinase A, which in turn induces the closure of gap junction channels (Piccolino et al, 1984; Lasater, 1987; DeVries and Schwartz, 1989; McMahon et al, 1989; Witkovsky and Schutte, 1991; Hampson et al, 1992; Bloomfield et al, 1997). Moreover, AII amacrine cells and ON cone BC coupling, a fundamental part of the rod pathway (Veruki and Hartveit, 2002), is modulated by nitric oxide, whose synthesis depends on light intensity (Vielma et al, 2012). This molecule activates the enzyme guanylate cyclase and increases cGMP levels producing the activation of PKG and the closure of gap junctions (Mills and Massey, 1995; Bloomfield and Volgyi, 2009).…”

Section: Discussionmentioning

confidence: 99%

Role of connexin channels in the retinal light response of a diurnal rodent

Palacios-Muñoz

Escobar

Vielma

et al. 2014

Front. Cell. Neurosci.

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Several studies have shown that connexin channels play an important role in retinal neural coding in nocturnal rodents. However, the contribution of these channels to signal processing in the retina of diurnal rodents remains unclear. To gain insight into this problem, we studied connexin expression and the contribution of connexin channels to the retinal light response in the diurnal rodent Octodon degus (degu) compared to rat, using in vivo ERG recording under scotopic and photopic light adaptation. Analysis of the degu genome showed that the common retinal connexins present a high degree of homology to orthologs expressed in other mammals, and expression of Cx36 and Cx43 was confirmed in degu retina. Cx36 localized mainly to the outer and inner plexiform layers (IPLs), while Cx43 was expressed mostly in cells of the retinal pigment epithelium. Under scotopic conditions, the b-wave response amplitude was strongly reduced by 18-β-glycyrrhetinic acid (β-GA) (−45.1% in degu, compared to −52.2% in rat), suggesting that connexins are modulating this response. Remarkably, under photopic adaptation, β-GA increased the ERG b-wave amplitude in degu (+107.2%) while reducing it in rat (−62.3%). Moreover, β-GA diminished the spontaneous action potential firing rate in ganglion cells (GCs) and increased the response latency of ON and OFF GCs. Our results support the notion that connexins exert a fine-tuning control of the retinal light response and have an important role in retinal neural coding.

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“…Retinal NO might modulate the neuronal communication between bipolar and ganglion cells, like the transient conversion of synaptic inhibition to excitation [Hoffpauir et al, 2006]. Amacrine cells, either NADPH-d reactive or NOSir, have been thoroughly reported in the retina of teleosts Pottek et al, 1997;Haamedi and Djamgoz, 2002], amphibians [Nöll et al, 1994;Kurenni et al, 1995;Blom et al, 2009], reptiles , birds [Fischer and Stell, 1999;Wilson et al, 2011;Tekmen-Clark and Gleason, 2013], and mammals [Vielma et al, 2012], representing a feature shared in all osteichthyes studied. Of note, holosteans, like cladistians, lack other nitrergic cells in the retina [López et al, 2016;present results].…”

Section: Retinamentioning

confidence: 99%

Pattern of Nitrergic Neuronal System Organization in the Brain of Two Holostean Fishes (Actinopterygii: Ginglymodi)

et al. 2017

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The study of the nitrergic system, formed by the networks of neurons containing the enzyme nitric oxide synthase (NOS), has been extremely useful in unraveling neuroanatomical features of the organization of the central nervous system of vertebrates. Thus, data are available for representatives of most vertebrate classes and, in particular, several studies have detailed the organization of this system in teleosts. In contrast, no information is available regarding this neurotransmission system in the brains of holosteans, an early diverged and poorly understood group of actinopterygian fishes, currently considered a sister group of teleosts that contains only 8 species. The present study provides the first detailed information on the distribution of nitrergic cell bodies and fibers in 2 holostean species of the genus Lepisosteus, the spotted gar L. oculatus and the Florida gar L. platyrhincus. NOS immunohistochemistry and the NADPH diaphorase (NADPH-d) histochemical reaction were used, and both techniques yielded identical results, with the exception of the primary olfactory and terminal nerve fibers, which only labeled for NADPH-d exclusively in L. oculatus. Double immunohistochemistry was conducted for the simultaneous detection of NOS with tyrosine hydroxylase, choline acetyltransferase, calbindin, calretinin, and serotonin to accurately establish the localization of the nitrergic neurons and fibers in the brain of holosteans, the neuroanatomy of which has been mostly neglected, and to assess possible interactions between these neuroactive substances. Distinct groups of nitrergic cells were located in subpallial areas, the basal hypothalamus, posterior tubercle, optic tectum and mesencephalic tegmentum, reticular formation, solitary tract nucleus, spinal cord, and amacrine cells in the retina. In addition, low numbers of nitrergic cells were observed in the pallium, suprachiasmatic nucleus, prethalamic and thalamic areas, torus lateralis and torus semicircularis, cerebellar and laterodorsal tegmental nuclei, and the ventral octavolateral area. Comparison of these results with those from other classes of vertebrates, and including a segmental analysis to correlate cell populations, reveals that the pattern of the nitrergic system in holosteans is very close to that in ancestral actinopterygian fishes and highlights conserved and derived traits.

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Nitric oxide signaling in the retina: What have we learned in two decades?

Cited by 71 publications

References 153 publications

Nitrosative Stress in the Rat Retina at the Onset of Streptozotocin-Induced Diabetes

Nitrosative Stress in the Rat Retina at the Onset of Streptozotocin-Induced Diabetes

Role of connexin channels in the retinal light response of a diurnal rodent

Pattern of Nitrergic Neuronal System Organization in the Brain of Two Holostean Fishes (Actinopterygii: Ginglymodi)

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