Elevated Glucose and Interleukin-1<i>β</i> Differentially Affect Retinal Microglial Cell Proliferation

Baptista, Filipa I.; Aveleira, Célia A.; Castilho, Áurea; Ambrósio, António Francisco

doi:10.1155/2017/4316316

Cited by 31 publications

(29 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A study using the BV-2 cell line showed that a shift from normal glucose (5mM) to high glucose (25 mM) enhanced microglia proliferation, secretion of pro-inflammatory factors (TNF-α and oxygen radicals) and stress proteins including heat shock protein 70 (HSP70), heme oxygenase 1 (HO-1) and inducible nitric oxide synthase (iNOS) ( 56 ). In a separate study, high glucose levels increased the production of IL-1β in retinal cell culture, which induced microglia cell proliferation ( 57 ). As microglia cells continue to proliferate in the high glucose environment, they may reprogram their checkpoints and respond by secreting more inflammatory factors.…”

Section: Morphological Analysis Of Microglia In Animal Models and Patmentioning

confidence: 99%

Microglia and Inflammatory Responses in Diabetic Retinopathy

2020

View full text Add to dashboard Cite

Diabetic retinopathy is a vision-threatening disease affecting neurons and microvasculature of the retina. The development of this disease is associated with the action of inflammatory factors that are connected to the activation of microglial cells, the resident tissue macrophages of the CNS. In the quiescent state, microglial cells help maintain tissue homeostasis in the retina through phagocytosis and control of low-grade inflammation. However, prolonged tissue stress due to hyperglycemia primes microglia to become overly reactive with the concomitant production of pro-inflammatory cytokines and chemokines causing chronic inflammation. In this review, we provide evidence of microglial cell activation and pro-inflammatory molecules associated with the development and progression of diabetic retinopathy. We further highlight innovative animal models that can mimic the disease in humans and discuss strategies in modulating microglial-mediated inflammation as potential therapeutic approaches in managing the disease.

show abstract

Section: Morphological Analysis Of Microglia In Animal Models and Patmentioning

confidence: 99%

Microglia and Inflammatory Responses in Diabetic Retinopathy

2020

View full text Add to dashboard Cite

show abstract

“…There are many works describing the microglial response to injury, activation mechanisms and phenotypes, and release of inflammatory mediators or their involvement in neurodegeneration and neuroprotection [ 27 – 33 ]. But little is known of their numerical and topographical dynamics and their correlation with the dying neurons, for instance, is the temporal and topographical course of PMC appearance regulated by the course of neuronal death?…”

Section: Introductionmentioning

confidence: 99%

Microglial dynamics after axotomy-induced retinal ganglion cell death

Nadal-Nicolás

Jiménez-López

Salinas‐Navarro

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundMicroglial cells (MCs) are the sentries of the central nervous system. In health, they are known as surveying MCs because they examine the tissue to maintain the homeostasis. In disease, they activate and, among other functions, become phagocytic to clean the cellular debris. In this work, we have studied the behavior of rat retinal MCs in two models of unilateral complete intraorbital optic nerve axotomy which elicit a different time course of retinal ganglion cell (RGC) loss.MethodsAlbino Sprague-Dawley rats were divided into these groups: (a) intact (no surgery), (b) fluorogold (FG) tracing from the superior colliculi, and (c) FG tracing + crush or transection of the left optic nerve. The retinas were dissected from 2 days to 2 months after the lesions (n = 4–12 group/lesion and time point) and then were subjected to Brn3a and Iba1 double immunodetection. In each intact retina, the total number of Brn3a+RGCs and Iba+MCs was quantified. In each traced retina (b and c groups), FG-traced RGCs and phagocytic microglial cells (PMCs, FG+Iba+) were also quantified. Topographical distribution was assessed by neighbor maps.ResultsIn intact retinas, surveying MCs are homogenously distributed in the ganglion cell layer and the inner plexiform layer. Independently of the axotomy model, RGC death occurs in two phases, one quick and one protracted, and there is a lineal and topographical correlation between the appearance of PMCs and the loss of traced RGCs. Furthermore, the clearance of FG+RGCs by PMCs occurs 3 days after the actual loss of Brn3a expression that marks RGC death. In addition, almost 50% of MCs from the inner plexiform layer migrate to the ganglion cell layer during the quick phase of RGC loss, returning to the inner plexiform layer during the slow degeneration phase. Finally, in contrast to what happens in mice, in rats, there is no microglial phagocytosis in the contralateral uninjured retina.ConclusionsAxotomy-induced RGC death occurs earlier than RGC clearance and there is an inverse correlation between RGC loss and PMC appearance, both numerically and topographically, suggesting that phagocytosis occurs as a direct response to RGC death rather than to axonal damage.

show abstract

“…Several reports have demonstrated the role of microglia in the loss of retinal ganglion cells and endothelial dysfunction with subsequent BRB breakdown in diabetic retinopathy ( Krady et al, 2005 ; Gaucher et al, 2007 ; Zeng et al, 2008 ; Grigsby et al, 2014 ; Goncalves et al, 2016 ; Sorrentino et al, 2016 ) ( Figure 3 ). Upon exposure to high glucose levels, microglia become reactive and secret pro-inflammatory mediators namely, TNF ( Costa et al, 2012 ) and IL-1β ( Krady et al, 2005 ; Baptista et al, 2017 ). These cytokines induce the dysfunction of the BRB by enhancing caspase-3 activity in endothelial cells.…”

Section: Crosstalk Between Endothelial and Retinal Cellsmentioning

confidence: 99%

Sweet Stress: Coping With Vascular Dysfunction in Diabetic Retinopathy

et al. 2018

Self Cite

View full text Add to dashboard Cite

Oxidative stress plays key roles in the pathogenesis of retinal diseases, such as diabetic retinopathy. Reactive oxygen species (ROS) are increased in the retina in diabetes and the antioxidant defense system is also compromised. Increased ROS stimulate the release of pro-inflammatory cytokines, promoting a chronic low-grade inflammation involving various signaling pathways. An excessive production of ROS can lead to retinal endothelial cell injury, increased microvascular permeability, and recruitment of inflammatory cells at the site of inflammation. Recent studies have started unraveling the complex crosstalk between retinal endothelial cells and neuroglial cells or leukocytes, via both cell-to-cell contact and secretion of cytokines. This crosstalk is essential for the maintenance of the integrity of retinal vascular structure. Under diabetic conditions, an aberrant interaction between endothelial cells and other resident cells of the retina or invading inflammatory cells takes place in the retina. Impairment in the secretion and flow of molecular signals between different cells can compromise the retinal vascular architecture and trigger angiogenesis. In this review, the synergistic contributions of redox-inflammatory processes for endothelial dysfunction in diabetic retinopathy will be examined, with particular attention paid to endothelial cell communication with other retinal cells.

show abstract

Elevated Glucose and Interleukin-1β Differentially Affect Retinal Microglial Cell Proliferation

Cited by 31 publications

References 62 publications

Microglia and Inflammatory Responses in Diabetic Retinopathy

Microglia and Inflammatory Responses in Diabetic Retinopathy

Microglial dynamics after axotomy-induced retinal ganglion cell death

Sweet Stress: Coping With Vascular Dysfunction in Diabetic Retinopathy

Contact Info

Product

Resources

About