Nitric Oxide Synthase Expression in Ischemic Rat Retinas

Kobayashi, Miwako; Kuroiwa, Toshihiko; Shimokawa, Reiko; Okeda, Riki; Tokoro, Takashi

doi:10.1016/s0021-5155(99)00220-8

Cited by 62 publications

(46 citation statements)

References 33 publications

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“…Whereas at 1 day after retinal ischemia NOS2 is expressed in leukocytes, resident retinal cells acquire expression of NOS2 several days after ischemia (39). Similarly, studies in patients and animals suggest that Muller cells express NOS2 in ischemic and diabetic retinopathies (66,67). The fact that Muller cells express CD40 and that CD40 stimulation can induce NOS2 and COX-2 expression (16,19) raises the possibility that direct engagement of CD40 in resident retinal cells may also result in NOS2 and/or COX-2 expression.…”

Section: Discussionmentioning

confidence: 99%

CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

Portillo

Grol

Zheng

et al. 2008

The Journal of Immunology

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Retinopathies are major causes of visual impairment. We used a model of ischemic retinopathy to examine the role of CD40 in the pathogenesis of retinal injury. Retinal inflammation, loss of ganglion cells, and capillary degeneration were markedly attenuated in ischemic retinas of CD40−/− mice. Up-regulation of NOS2 and COX2 after retinal ischemia were blunted in CD40−/− mice. NOS2-COX-2 up-regulation in ischemic retinas from wild-type mice was at least in part explained by recruitment of NOS2+COX-2+ leukocytes. Up-regulation of KC/CXCL1 and ICAM-1 also required CD40. Retinal endothelial and Muller cells expressed CD40. Stimulation of these cells through CD40 caused ICAM-1 up-regulation and KC/CXCL1 production. Bone marrow transplant experiments revealed that leukocyte infiltration, ganglion cell loss, and up-regulation of proinflammatory molecules after retinal ischemia were dependent on CD40 expression in the retina and not peripheral blood leukocytes. These studies identified CD40 as a regulator of retinal inflammation and neurovascular degeneration. They support a model in which CD40 stimulation of endothelial and Muller cells triggers adhesion molecule up-regulation and chemokine production, promoting the recruitment of leukocytes that express NOS2/COX-2, molecules linked to neurovascular degeneration.

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Section: Discussionmentioning

confidence: 99%

CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

Portillo

Grol

Zheng

et al. 2008

The Journal of Immunology

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“…Retinal ischaemia induced by common carotid artery occlusion in rats induced iNOS expression in Mü ller cells and retinal ganglion cells. 34 In a murine model of oxygen-induced retinopathy of prematurity, iNOS mRNA was expressed in ischaemic retina. 35 In a previous study we have shown iNOS immunoreactivity in retinal Mü ller glial cells from human patients with diabetes and nonproliferative diabetic retinopathy using immunohistochemistry and heat-induced antigen retrieval with a microwave oven and 30 min incubation with the antibody.…”

Section: Discussionmentioning

confidence: 99%

“…This colocalization can be explained in two ways, either through a common induction pathway or through a sequential relation in time between both molecules. Ischaemia has been shown to induce the expression of iNOS 34,35 and VEGF 36 in the ischaemic retina. Yet, other studies demonstrated that VEGF induced the expression of iNOS in human endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Inducible nitric oxide synthase and vascular endothelial growth factor are colocalized in the retinas of human subjects with diabetes

El-Asrar

Meersschaert

Dralands

et al. 2004

Eye

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“…Rather, the inducible form of nitric oxide synthase (iNOS) is now expressed by glial cells, which causes an increased exposure of the neurones to ROS. 52 Finally, the pathological scenario involves a dramatic change in the cytokine release pattern of the Mü ller cells (Figure 2b, IV). Oedema/pressure-mediated reduction of retinal blood flow and excitotoxic overstimulation of neuronal metabolism contribute to retinal hypoxia which stimulates the release of VEGF from Mü ller cells 53 and retinal pigment epithelial (RPE) cells.…”

Section: Mü Ller Cells and Retinopathymentioning

confidence: 99%

Glia: the fulcrum of brain diseases

et al. 2007

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Neuroglia represented by astrocytes, oligodendrocytes and microglial cells provide for numerous vital functions. Glial cells shape the micro-architecture of the brain matter; they are involved in information transfer by virtue of numerous plasmalemmal receptors and channels; they receive synaptic inputs; they are able to release 'glio'transmitters and produce long-range information exchange; finally they act as pluripotent neural precursors and some of them can even act as stem cells, which provide for adult neurogenesis. Recent advances in gliology emphasised the role of glia in the progression and handling of the insults to the nervous system. The brain pathology, is, to a very great extent, a pathology of glia, which, when falling to function properly, determines the degree of neuronal death, the outcome and the scale of neurological deficit. Glial cells are central in providing for brain homeostasis. As a result glia appears as a brain warden, and as such it is intrinsically endowed with two opposite features: it protects the nervous tissue as long as it can, but it also can rapidly assume the guise of a natural killer, trying to eliminate and seal the damaged area, to save the whole at the expense of the part. The sudden emergence of an intellect, and therefore a human being, which materialised only around a million years ago, remains the main mystery for our self-understanding. Similarly, we still do not know by which steps or transitions the human intellect emerged from the animal kingdom and where the fundamental difference between a man and an animal lies. According to the neuronal doctrine, which governs modern neuroscience since the beginning of the twentieth century, 1,2 the neurone is regarded as a basic information processing unit consisting of dendrites and axons with a unidirectional flow of information from the receiving dendrites via the integrating cell body to the terminal branches of the axon. Neuronal networks, connected through synaptic contacts, are generally considered as the substrate of our intellect.The number and size of neural cells increase with the size of the body and of the brain of mammals. This increasing quantity eventually has caused the generation of a new quality, the intellect. Rather amazingly, however, there is a relatively little difference in the morphology and physiology of neurones between humans and beasts; similarly the density of synaptic contacts in the brains of rodents and humans is more or less constant at around 1100-1300 millions/mm 3 . 3 On the contrary, evolution of the nervous system resulted in great changes in the second type of neural cells, the neuroglia. 4 Indeed, phylogenetic advance in brain complexity and capabilities coincided with a remarkable increase in the number of glial cells: in the rodent cortex the glial to neurone ratio is about 0.3 : 1, whereas in humans the same ratio is several times higher being B1.65:1, 5 while the total number of glial cells in the human brain is B10 (or even more) times larger than in lesser mammals. Astrocytes ...

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Nitric Oxide Synthase Expression in Ischemic Rat Retinas

Cited by 62 publications

References 33 publications

CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

CD40 Mediates Retinal Inflammation and Neurovascular Degeneration

Inducible nitric oxide synthase and vascular endothelial growth factor are colocalized in the retinas of human subjects with diabetes

Glia: the fulcrum of brain diseases

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