Effect of Müller cell co-culture on in vitro permeability of bovine retinal vascular endothelium in normoxic and hypoxic conditions

Tretiach, Marina; Madigan, Michele C.; Wen, Li; Gillies, Mark C

doi:10.1016/j.neulet.2004.12.026

Cited by 56 publications

(33 citation statements)

References 18 publications

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“…Coculturing Müller cells and primary bovine endothelial cell monolayers improved barrier function in normoxic conditions but led to barrier breakdown under hypoxic conditions. 36 Inducing breakdown of BRB breakdown in rats by disrupting Müller cells with subretinal injection of DL-alpha-AAA 37 resulted in vascular changes in association with reduced expression of claudin 5 that were observed predominantly in areas of Müller-cell disruption. 37 These observations, along with downregulation of tight junction pathways found in the present study support the concept that Müller-cell deficiency disturbs retinal vascular interendothelial tight junctions.…”

Section: Discussionmentioning

confidence: 99%

Differential Gene Expression Profiling after Conditional Müller-Cell Ablation in a Novel Transgenic Model

Chung

Shen

Jayawardana

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Müller cells, the principal glial cells in the mammalian retina, play an important role in the maintenance of retinal homeostasis. Recent reports suggest that Müller-cell dysfunction may contribute to the pathogenesis of retinal diseases such as idiopathic macular telangiectasia type 2. In the present study, we used microarray to compare retinae isolated from transgenic mice in which the Müller cells of adult mice retinae can be selectively ablated with control mice.METHODS. Retinae were isolated 1 week, 1 month, and 3 months after tamoxifen-induced selective Müller-cell ablation and microarray were performed with Affymatrix microarrays. Differentially expressed (DE) genes, temporal trends of DE genes, and pathway analysis were conducted. Quantitative realtime polymerase chain reaction (qRT-PCR) was performed to validate the results.RESULTS. Strong upregulation of mRNA of proteins involved in gliosis, apoptosis, and neurotrophism was found 1 week after ablation and their related pathways such as the apoptotic and Jak/Stat pathways were identified. Three months after induced Müller-cell ablation, Müller-cell metabolic pathways and vasculopathy-related pathways such as genes involved in glycolysis and tight junctions were downregulated. qRT-PCR analysis showed consistent expression trends of selected genes. CONCLUSIONS.The results were generally consistent with the previous morphologic findings in this model, in which photoreceptor degeneration soon after Müller-cell ablation, accompanied by blood-retinal barrier breakdown and subsequent retinal neovascularization were reported. These results are consistent with a significant contribution of Müller-cell dysfunction on retinal neuronal injury and vascular pathology at the mRNA level. (Invest Ophthalmol Vis Sci.

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Section: Discussionmentioning

confidence: 99%

Differential Gene Expression Profiling after Conditional Müller-Cell Ablation in a Novel Transgenic Model

Chung

Shen

Jayawardana

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…They are involved in the control and homeostasis of K + and other ions signaling molecules, and in the control of extracellular pH [60]. Dysfunction of Müller cells may contribute to a breakdown of the iBRB in many pathological conditions, such as diabetes [61]. Müller cells enhance the secretion of VEGF under hypoxic and inflammatory conditions [62,63].…”

Section: Blood-retinal Barriermentioning

confidence: 99%

Recent Advances in Ocular Drug Delivery Systems

2011

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Abstract:Transport of drugs applied by traditional dosage forms is restricted to the eye, and therapeutic drug concentrations in the target tissues are not maintained for a long duration since the eyes are protected by a unique anatomy and physiology. For the treatment of the anterior segment of the eye, various droppable products to prolong the retention time on the ocular surface have been introduced in the market. On the other hand, direct intravitreal implants, using biodegradable or non-biodegradable polymer technology, have been widely investigated for the treatment of chronic vitreoretinal diseases. There is urgent need to develop ocular drug delivery systems which provide controlled release for the treatment of chronic diseases, and increase patient's and doctor's convenience to reduce the dosing frequency and invasive treatment. In this article, progress of ocular drug delivery systems under clinical trials and in late experimental stage is reviewed.

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“…before microvacular lesions can be detected in ophthalmologic examination. In addition, neuroretinal degeneration will initiate and/or activate several metabolic and signalling pathways which will participate in the microangiopathic process as well as in the disruption of the blood-retinal barrier (a crucial element in the pathogenesis of DR) [11] . The underlying mechanisms that lead to neuronal deficits are likely to be broad.…”

Section: Introductionmentioning

confidence: 99%

Neurodegeneration: An early event of diabetic retinopathy

Villarroel

Ciudin²,

Hernández³

et al. 2010

WJD

132

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Diabetic retinopathy (DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia. However, retinal neurodegeneration is already present before any microcirculatory abn ormalities can be detected in ophthalmoscopic exa mination. In other words, retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR. Elevated levels of glutamate and the overexpression of the renin angiotensinsystem play an essential role in the neurodegenerative process that occurs in diabetic retina. Among neuroprotective factors, pigment epithelial derived factor, somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review. Nevertheless, it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neu rotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye. New strategies, based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors, are currently being tested in experimental models and in clinical pilot studies. Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.

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Effect of Müller cell co-culture on in vitro permeability of bovine retinal vascular endothelium in normoxic and hypoxic conditions

Cited by 56 publications

References 18 publications

Differential Gene Expression Profiling after Conditional Müller-Cell Ablation in a Novel Transgenic Model

Differential Gene Expression Profiling after Conditional Müller-Cell Ablation in a Novel Transgenic Model

Recent Advances in Ocular Drug Delivery Systems

Neurodegeneration: An early event of diabetic retinopathy

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