Activated human retinal microglia under pathological conditions

Vrabec, F

doi:10.1007/bf00410026

Cited by 21 publications

(12 citation statements)

References 11 publications

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“…These less ramified microglia increased in numbers until the terminal stage of the disease. Such morphological changes are generally considered to reflect progression to a functionally ''activated'' phenotype (Thomas, 1992;Vrabec, 1975). An apparent redistribution of microglia toward the retinal vessels began around day 3 p.i.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of microglia has been reported in numerous CNS pathologies including Alzheimer's disease (Giulian et al, 1995;McGeer et al, 1994;Nieto and Mora, 1994), AIDS encephalopathy (Gelman, 1993;Vazeux, 1991), multiple sclerosis (Newcombe et al, 1994;Selmaj et al, 1991), and its animal model experimental autoimmune encephalomyelitis (Bauer et al, 1995;Renno et al, 1995). In this activated condition, microglia may assume a macrophage-like morphology characterized by a larger, irregularly shaped soma with pseudopodia, lacking the ramified processes of the resting form found in normal CNS tissue (Thomas, 1992;Vrabec, 1975). In the activated state microglia are thought to produce reactive oxygen species (Colton and Gilbert, 1987;Sonderer et al, 1987) and secrete, as well as respond to, several cytokines (Benveniste, 1992), which, as mentioned earlier, are essential to the development of FMCM.…”

Section: Introductionmentioning

confidence: 96%

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Early activation of microglia in the pathogenesis of fatal murine cerebral malaria

Medana

Hunt

Chan‐Ling

1997

Glia

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Early activation of microglia in the pathogenesis of fatal murine cerebral malaria

Medana

Hunt

Chan‐Ling

1997

Glia

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“…Microglia are equipped with an array of molecular pattern recognition receptors and scavenger receptors that allow them to recognize and react to the presence of "nonself," such as pathogens, and to "altered self," such as damaged and apoptotic neurons [164]. The term microglial activation initially referred to an extreme response to pathogens resulting in a highly inflammatory phenotype with amoeboid morphology and increased motility [168,169]. This classically activated phenotype includes production of inflammatory cytokines, proteases, nitric oxide (NO • ) and reactive oxygen species (ROS).…”

Section: Possible Causes Of Retinal Neuroinflammation In Drmentioning

confidence: 99%

Angiogenic Factors and Cytokines in Diabetic Retinopathy

Abcouwer¹

2011

J Clin Cell Immunol

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Diabetic retinopathy (DR) is a sight-threatening complication of both type-1 and type-2 diabetes. The recent success of treatments inhibiting the function of vascular endothelial growth factor (VEGF) demonstrates that specific targeting of a growth factor responsible for vascular permeability and growth is an effective means of treating DRtargets involved in the control of retinal vascular function. However, additional treatment options and preventative measures are still needed and these require a greater understanding of the pathological mechanisms leading to the disturbance of retinal tissue homeostasis in DR. Although severe DR can be treated as a vascular disease, abundant data suggests that inflammation is also occurring in the diabetic retina.Thus, anti-inflammatory therapies may also be useful for treatment and prevention of DR. Herein, the evidence for altered expression of angiogenic factors and cytokines in DR is reviewed and possible mechanisms by which the expression of VEGF and cytokines may be increased in the diabetic retina are examined. In addition, the potential role for microglial activation in diabetic retinal neuroinflammation is explored.

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“…Recruitment of microglia/monocytes to damaged regions occurs in almost every pathological condition in the CNS [10,11], and is apparent in a range of prominent human retinal pathologies including age-related macular degeneration (AMD) [2,12-15], retinitis pigmentosa [2], late-onset retinal degeneration [2], retinal detachment [16], glaucoma [17-19], and diabetic retinopathy [17,20], as well as in many experimental models of retinal degeneration [9]. Despite their beneficial properties, widespread recruitment and activation of microglia may damage neurons [21-25], probably through their secretion of pro-inflammatory mediators and cytotoxic factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β [10,26,27], and nitric oxide [23,28,29].…”

Section: Introductionmentioning

confidence: 99%

Small interfering RNA-mediated suppression of Ccl2 in Müller cells attenuates microglial recruitment and photoreceptor death following retinal degeneration

Rutar

Natoli

Provis

2012

J Neuroinflammation

102

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BackgroundThe recruitment and activation of inflammatory cells is thought to exacerbate photoreceptor death in retinal degenerative conditions such as age-related macular degeneration (AMD). We investigated the role of Müller cell-derived chemokine (C-C motif) ligand (Ccl)2 expression on monocyte/microglia infiltration and photoreceptor death in light-mediated retinal degeneration, using targeted small interfering (si)RNA.MethodsAdult Sprague–Dawley rats were injected intravitreally with 1 μg of either Ccl2 siRNA or scrambled siRNA, and were then exposed to 1000 lux of light for a period of 24 hours. The mice were given an overdose of barbiturate, and the retinas harvested and evaluated for the effects of bright-light exposure. Ccl2 expression was assessed by quantitative PCR, immunohistochemistry, and in situ hybridization. Monocytes/microglia were counted on retinal cryostat sections immunolabeled with the markers ED1 and ionized calcium binding adaptor (IBA)1, and photoreceptor apoptosis was assessed using terminal dUTP nick end labeling.ResultsIntravitreal injection of Ccl2 siRNA significantly reduced the expression of Ccl2 following light damage to 29% compared with controls. In retinas injected with Ccl2 siRNA, in situ hybridization and immunohistochemistry on retinal cryostat sections showed a substantial decrease in Ccl2 within Müller cells. Cell counts showed significantly fewer ED1-positive and IBA1-positive cells in the retinal vasculature and outer nuclear layer of Ccl2 siRNA-injected retinas, compared with controls. Moreover, there was significantly less photoreceptor apoptosis in Ccl2 siRNA-injected retinas compared with controls.ConclusionsOur data indicate that Ccl2 expression by Müller cells promotes the infiltration of monocytes/microglia, thereby contributing to the neuroinflammatory response and photoreceptor death following retinal injury. Modulation of exaggerated chemokine responses using siRNA may have value in reducing inflammation-mediated cell death in retinal degenerative disease such as AMD.

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Activated human retinal microglia under pathological conditions

Cited by 21 publications

References 11 publications

Early activation of microglia in the pathogenesis of fatal murine cerebral malaria

Early activation of microglia in the pathogenesis of fatal murine cerebral malaria

Angiogenic Factors and Cytokines in Diabetic Retinopathy

Small interfering RNA-mediated suppression of Ccl2 in Müller cells attenuates microglial recruitment and photoreceptor death following retinal degeneration

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