NO signaling in retinal bipolar cells

Agurto, Adolfo; Vielma, Alex H.; Cadiz, Bárbara; Couve, Eduardo; Schmachtenberg, Oliver

doi:10.1016/j.exer.2017.05.013

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…Also, the colocalisation of nitrotyrosine and apoptosis in, and proximal to amacrine cells of the INL, may be related to the fact that the majority of NOS-dependent retinal neurons reside in the INL. In this regard it is significant that the amacrine cells that predominate at the inner aspect of the INL represent the main class of nNOS-dependent neurons in the retina, with some, but less nNOS expression in bipolar cells 1 , 2 , 7 , 48 . Therefore, it is reasonable to propose that local NO production by nNOS expressing neurons represents the source of the INL peroxynitrite, which causes nitro-oxidative damage and cell death in the source cells.…”

Section: Discussionmentioning

confidence: 99%

BH4 supplementation reduces retinal cell death in ischaemic retinopathy

Edgar,

Cunning,

Gardiner

et al. 2023

Sci Rep

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Dysregulation of nitric oxide (NO) production can cause ischaemic retinal injury and result in blindness. How this dysregulation occurs is poorly understood but thought to be due to an impairment in NO synthase function (NOS) and nitro-oxidative stress. Here we investigated the possibility of correcting this defective NOS activity by supplementation with the cofactor tetrahydrobiopterin, BH4. Retinal ischaemia was examined using the oxygen-induced retinopathy model and BH4 deficient Hph-1 mice used to establish the relationship between NOS activity and BH4. Mice were treated with the stable BH4 precursor sepiapterin at the onset of hypoxia and their retinas assessed 48 h later. HPLC analysis confirmed elevated BH4 levels in all sepiapterin supplemented groups and increased NOS activity. Sepiapterin treatment caused a significant decrease in neuronal cell death in the inner nuclear layer that was most notable in WT animals and was associated with significantly diminished superoxide and local peroxynitrite formation. Interestingly, sepiapterin also increased inflammatory cytokine levels but not microglia cell number. BH4 supplementation by sepiapterin improved both redox state and neuronal survival during retinal ischaemia, in spite of a paradoxical increase in inflammatory cytokines. This implicates nitro-oxidative stress in retinal neurones as the cytotoxic element in ischaemia, rather than enhanced pro-inflammatory signalling.

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Section: Discussionmentioning

confidence: 99%

BH4 supplementation reduces retinal cell death in ischaemic retinopathy

Edgar,

Cunning,

Gardiner

et al. 2023

Sci Rep

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“…In our previous studies, we were able to show, on one hand, that the loss of bipolar cells induced by H 2 O 2 could also be prevented by hypothermia treatment [ 6 ] and, on the other hand, hypoxic stress also led to a loss of bipolar cells only in the late point in time, which was prevented by 1400 W [ 5 ]. Results of other studies suggest that bipolar cells represent NO sources in the inner retina and are involved in physiological and pathological processes of the inner retina via NO signal transmissions [ 53 ]. Thus, inhibition of iNOS seems to be an option to protect bipolar cells from an excessive amount of NO and thus maintain the signaling between photoreceptors and RGCs.…”

Section: Discussionmentioning

confidence: 99%

Reduced Retinal Degeneration in an Oxidative Stress Organ Culture Model through an iNOS-Inhibitor

Mueller‐Buehl

Tsai

Hurst

et al. 2021

Biology

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In retinal organ cultures, H2O2 can be used to simulate oxidative stress, which plays a role in the development of several retinal diseases including glaucoma. We investigated whether processes underlying oxidative stress can be prevented in retinal organ cultures by an inducible nitric oxide synthase (iNOS)-inhibitor. To this end, porcine retinal explants were cultivated for four and eight days. Oxidative stress was induced via 300 µM H2O2 on day one for three hours. Treatment with the iNOS-inhibitor 1400 W was applied simultaneously, remaining for 72 h. Retinal ganglion cells (RGC), bipolar and amacrine cells, apoptosis, autophagy, and hypoxia were evaluated immunohistologically and by RT-qPCR. Additionally, RGC morphology was analyzed via transmission electron microscopy. H2O2-induced RGCs loss after four days was prevented by the iNOS-inhibitor. Additionally, electron microscopy revealed a preservation from oxidative stress in iNOS-inhibitor treated retinas at four and eight days. A late rescue of bipolar cells was seen in iNOS-inhibitor treated retinas after eight days. Hypoxic stress and apoptosis almost reached the control situation after iNOS-inhibitor treatment, especially after four days. In sum, the iNOS-inhibitor was able to prevent strong H2O-induced degeneration in porcine retinas. Hence, this inhibitor seems to be a promising treatment option for retinal diseases.

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“…It was observed in neurons and the pigment epithelium, indicating a role in the development or protection from infection in the ganglion cell layer and in the nuclear layers of the retina [ 42 , 43 ]. It has been suggested that amacrine cells may be the most prominent source for NO but has also been sourced from certain bipolar cells, which implies involvement in both in the physiological and pathological processes here as well [ 43 , 44 ]. Other studies have demonstrated that NO acts as a vascular endothelial relaxant involved in normal retinal blood flow control, as well as related to several ocular diseases associated with oxidative stress, including retinitis pigmentosa, diabetic retinopathy, glaucoma and AMD [ 42 , 43 , 44 ].…”

Section: No In the Retinamentioning

confidence: 99%

Nitric Oxide Interaction with the Eye

Erdinest

London²,

Ovadia

et al. 2021

Vision

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Nitric oxide (NO) is acknowledged as a vital intercellular messenger in multiple systems in the body. Medicine has focused on its functions and therapeutic applications for decades, especially in cardiovascular and nervous systems, and its role in immunological responses. This review was composed to demonstrate the prevalence of NO in components of the ocular system, including corneal cells and multiple cells in the retina. It discussed NO’s assistance during the immune, inflammation and wound-healing processes. NO is identified as a vascular endothelial relaxant that can alter the choroidal blood flow and prompt or suppress vascular changes in age-related macular degeneration and diabetes, as well as the blood supply to the optic nerve, possibly influencing the progression of glaucoma. It will provide a deeper understanding of the role of NO in ocular homeostasis, the delicate balance between overproduction or underproduction and the effect on the processes from aqueous outflow and subsequent intraocular pressure to axial elongation and the development of myopia. This review also recognized the research and investigation of therapies being developed to target the NO complex and treat various ocular diseases.

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NO signaling in retinal bipolar cells

Cited by 7 publications

References 39 publications

BH4 supplementation reduces retinal cell death in ischaemic retinopathy

BH4 supplementation reduces retinal cell death in ischaemic retinopathy

Reduced Retinal Degeneration in an Oxidative Stress Organ Culture Model through an iNOS-Inhibitor

Nitric Oxide Interaction with the Eye

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