High glucose enhances intracellular Ca2+ responses triggered by purinergic stimulation in retinal neurons and microglia

Calcium mediates high glucose-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells through CaMKII-CREB pathway

“…In this context, recent studies using conditional KO mice models have suggested that the Müller cell-derived HIF-1α and VEGF has a causative role in the major pathologic changes in DR [27,28] . Increasing evidence suggests that hyperglycemia induces changes in the retinal [Ca 2+ ] i dynamics [2,4] , which have been associated with distinct pathological processes, such as DR. Here, using retinal Müller cells cultured in vitro, we have demonstrated that the increased [Ca 2+ ] i is associated with aberrant HG-induced expression of HIF-1α and VEGF because increased [Ca 2+ ] i is an ubiquitous signal controlling gene expression [9,10,29,30] .…”

“…Hyperglycemia is a pathological hallmark of diabetic complications, such as diabetic retinopathy (DR), and hyperglycemia can also increase the intracellular free calcium concentration ([Ca 2+ ] i ) in various cell types [1][2][3][4] . An increase in [Ca 2+ ] i has been shown to play an important role in the pathogenesis of angiogenesis [5,6] , which is the most common cause of blindness in DR. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors produced by retinal ischemia [7] .…”

Enhancement of LPS-Induced Microglial Inflammation Response via TLR4 Under High Glucose Conditions

“…High glucose has been shown to induce inflammatory cytokines, chemokines, p38 mitogen-activated protein kinase, reactive oxygen species (ROS), protein kinase C (PKC), and NF-kB activity in both clinical and experimental systems [29,30,31,32]. It is known that high glucose can enhance the intracellular Ca 2+ response triggered by purinergic stimulation in neurons and microglia [33] and can induce TLR2 and TLR4 expression via PKC-α and PKC-γ, respectively in human monocytes[34]. Our study provides new information on the combined impact of LPS and hyperglycemia in microglia.…”

Long-term exposure to high glucose increases the content of several exocytotic proteins and of vesicular GABA transporter in cultured retinal neural cells

“…Moreover, in high glucose-treated cells, the increase in [Ca 2+ ] i triggered by KCl, kainate or purinergic P2 receptors activation is enhanced and the recovery to basal Ca 2+ levels is delayed [18,19], which may account for the increase in neurotransmitter release from retinal neurons. In the retinas of diabetic animals, the release of [ 3 H]d-aspartate evoked by KCl is increased after 4 weeks of diabetes, comparing to the retinas of age-matched control animals [16].…”