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

Li, Jun; Wang, Peipei; Yu, Songping; Zheng, Zhi; Xu, Xun

doi:10.1038/aps.2012.61

Cited by 40 publications

(32 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation is supported by previous studies with retinal cells, where hyperglycemic conditions increased VEGF abundance (10,37,38). Herein we extend the previous studies to demonstrate that the effect is also dependent on REDD1.…”

Section: Discussionsupporting

confidence: 91%

Regulated in Development and DNA Damage 1 Is Necessary for Hyperglycemia-induced Vascular Endothelial Growth Factor Expression in the Retina of Diabetic Rodents

Dennis

Kimball

Fort

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: VEGF plays a causal role in diabetic retinopathy. Results: Hyperglycemia induced VEGF and REDD1 expression in the retina of wild-type, but not REDD1 knock-out mice. Conclusion: REDD1 is necessary for hyperglycemia mediated effects on VEGF expression in the retina of diabetic mice. Significance: Molecular therapies targeting REDD1 could prove useful in preventing pathological effects of hyperglycemia.

show abstract

Section: Discussionsupporting

confidence: 91%

Regulated in Development and DNA Damage 1 Is Necessary for Hyperglycemia-induced Vascular Endothelial Growth Factor Expression in the Retina of Diabetic Rodents

Dennis

Kimball

Fort

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Moreover, calcium contributes to the high-glucose-induced expression of the angiogenic factors HIF-1a and VEGF by retinal Müller cells. The activation of the CaMKII-CREB pathway by high-glucose may be a possible mechanism underlying the pathogenesis of diabetic retinopathy (Li et al, 2012).…”

Section: Gliosismentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

593

533

View full text Add to dashboard Cite

The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

show abstract

“…For primary culture studies, rat retinal Müller cells were obtained and identified as described previously [25]. Briefly, Sprague-Dawley rats at postnatal (PN) day 5 to PN7 were sacrificed and the enucleated eyes were washed under sterile conditions, and the anterior portions were discarded.…”

Section: Cell Culturementioning

confidence: 99%

Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes

Li¹,

Wang²,

Jia³

et al. 2016

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background: Curcumin possesses many pharmacological properties including anti-inflammatory effects. Although prior studies indicate that curcumin has beneficial effects for diabetic retinopathy, the mechanism of action is not known. To address this issue, we investigated the effect of curcumin against diabetes-induced retinal vascular damage and its mechanism of action by using cultured retinal Müller cells stimulated with high glucose. Methods: We studied the effects of curcumin in vivo in the retinas of rats rendered diabetic by streptozotocin and in vitro in Müller cells stimulated with high glucose. We administered curcumin, or KN93, an inhibitor of calcium/calmodulin dependent protein kinase II (CaMKII), or saline vehicle to experimental animals on a daily basis for 12 weeks. Primary cultures of rat Müller cells were incubated with normal glucose or high glucose, with or without curcumin, KN93, or pyrrolidine dithiocarbamate (PDTC), an inhibitor of the transcription protein nuclear factor κB (NF-κB). We examined mRNA and protein levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) by real-time RT-PCR and Western blotting, respectively. Retinal levels of CaMKII and NF-κB were examined by Western blotting. Vascular leakage was evaluated using Evans blue. Results: Curcumin and KN93 significantly inhibited the activation of CaMKII/NF-κB signaling induced by diabetes or elevated glucose, and subsequently decreased the expression of VEGF, iNOS and ICAM-1. These changes were associated with a decrease of diabetes-induced retinal vascular leakage. Conclusion: Curcumin protects the diabetic rat retina against early retinal vascular damage, by inhibition of CaMKII activity. Curcumin is currently used to treat a number of clinical conditions, and may prove beneficial for the management of diabetic retinopathy.

show abstract

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

Abstract: Aim: To investigate the effects of high glucose (HG) medium on expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in cultured rat retinal Müller cells and to determine the signaling pathways mediating the effects.

Cited by 40 publications

References 32 publications

Regulated in Development and DNA Damage 1 Is Necessary for Hyperglycemia-induced Vascular Endothelial Growth Factor Expression in the Retina of Diabetic Rodents

Regulated in Development and DNA Damage 1 Is Necessary for Hyperglycemia-induced Vascular Endothelial Growth Factor Expression in the Retina of Diabetic Rodents

Glia–neuron interactions in the mammalian retina

Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity in Streptozotocin-Induced Diabetes

Contact Info

Product

Resources

About