Characterization of nitric oxide signaling pathways in the mouse retina

Blom, Jan; Giove, Tom; Deshpande, Monika; Eldred, William D.

doi:10.1002/cne.23148

Cited by 37 publications

(43 citation statements)

References 35 publications

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“…NO mediates its effects through the production of cGMP from the enzyme NO-sensitive sGC [12, 13]. In the retina, the NO-cGMP pathway is involved in the modulation of visual information processing.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Thus, nitrergic ganglion cells and photoreceptors have been reported in the retina of teleosts Pottek et al, 1997;Ota et al, 1999;Haamedi and Djamgoz, 2002;Gaikwad et al, 2009], amphibians [Nöll et al, 1994;Kurenni et al, 1995;Blom et al, 2009], reptiles [Blute et al, 1997], birds [Fischer and Stell, 1999;Wilson et al, 2011;Tekmen-Clark and Gleason, 2013], and mammals [Blom et al, 2012], where protoreceptor cells always lack nitrergic labeling. Furthermore, nitrergic bipolar neurons have been described in the retina of chondrichthyes [Shiells and Falk, 1992], amphibians [Nöll et al, 1994;Kurenni et al, 1995;Blom et al, 2009], and reptiles [Cao and Eldred, 2001], whereas horizontal nitrergic cells have been reported only in teleosts [Ota et al, 1999;Haamedi and Djamgoz, 2002] and reptiles [Haverkamp and Eldred, 1998;Cuenca et al, 2000].…”

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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“…Then GC pathway will be triggered in on-bipolar cells. Besides in amacrine cell-ganglion cell-bipolar cell synapse; NO produced in amacrine cell, diffuse to the ganglion cell and activate the GC and this cause depolarization [31,32]. Depolarization in the retina is an essential step for seeing.…”

Section: Roles Of Noss In Seeing and Retinal Functionmentioning

confidence: 99%

Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases

Dagdeviren¹

2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

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Nitric oxide synthase has three isoforms; according to their roles and tissues or cells they are involved. Neuronal NOS (nNOS) takes place in neuronal signalling, endothelial NOS (eNOS) takes place in vasodilation and inducible NOS (iNOS) takes place in immune responses. nNOS and eNOS are dominant but all isoforms have various roles in the central nervous system. nNOS and eNOS separately or together works in healthy brain during cognitive processes and in unhealthy brain during the pathology of related diseases. These roles were shown by inhibitor applied or by transgenic animal model studies and also by investigating the diseases at the molecular level. Besides, it is possible to say that iNOS has roles in some neurological pathologies creating immune responses. Three different isoforms mainly serve in different systems so there are lots of researchers from various disciplines working collaterally not knowing the others related works about NOSs. Because of this, a comprehensive chapter will be valuable for neuroscientists working with either healthy or unhealthy brains. The purpose of this chapter is to gather an overview of NOSs duties during the normal processes of the brain like learning and memory formation and abnormal processes such as depression, schizophrenia and brain cancers.

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Characterization of nitric oxide signaling pathways in the mouse retina

Cited by 37 publications

References 35 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

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

Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases

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