Purinergic signaling in retinal degeneration and regeneration

Reichenbach, Andreas; Bringmann, Andreas

doi:10.1016/j.neuropharm.2015.05.005

Cited by 65 publications

(70 citation statements)

References 207 publications

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“…45 The retinal P2X7R is overactivated in diabetes, leading to pathological gliosis. 118 Furthermore, both degeneration of the retinal pigment epithelium and choroidal neovascularization associated with different types of age-related macular degeneration are dependent on the P2X7R. 118 Thus, P2X7R antagonists might prove useful in treating these conditions.…”

Section: P2xr Modulators As Drug Targets In the Eyementioning

confidence: 99%

“…118 Furthermore, both degeneration of the retinal pigment epithelium and choroidal neovascularization associated with different types of age-related macular degeneration are dependent on the P2X7R. 118 Thus, P2X7R antagonists might prove useful in treating these conditions. Nonnucleotide P2X3R antagonists are proceeding toward the clinic for treatment of cough, 119 and P2X4R antagonist (structure not disclosed) is scheduled to enter clinical trials for chronic neuropathic pain.…”

Section: P2xr Modulators As Drug Targets In the Eyementioning

confidence: 99%

“…122 Antagonists of the P2X7R prevent neuronal apoptosis in the retina induced by ATP or by hypoxia. 118,[123][124][125][126]127,128 Such antagonists include Brilliant Blue G (BBG, structure not shown) and MRS 2540 91. JNJ-47965567 96 is a CNS penetrant, selective P2X7R antagonist, while JNJ-54173717 97 was recently reported as a PET ligand for imaging the P2X7R.…”

Section: P2xr Modulators As Drug Targets In the Eyementioning

confidence: 99%

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Ocular Purine Receptors as Drug Targets in the Eye

Civan

2016

Journal of Ocular Pharmacology and Therapeutics

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Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A 1 , A 2A , and A 3 . An A 1 AR agonist is in clinical trials for glaucoma, A 2A AR reduces neuroinflammation, A 3 AR protects retinal ganglion cells from apoptosis, and both A 3 AR agonists and antagonists had been reported to lower intraocular pressure (IOP). Extracellular concentrations of endogenous nucleotides, including dinucleoside polyphosphates, are increased in pathological states, activating P2Y and P2XRs throughout the eye. P2YR agonists, including P2Y 2 and P2Y 6 , lower IOP. Antagonists of the P2X7R prevent the ATP-induced neuronal apoptosis in the retina. Thus, modulators of the purinome in the eye might be a source of new therapies for ocular diseases.

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Section: P2xr Modulators As Drug Targets In the Eyementioning

confidence: 99%

Section: P2xr Modulators As Drug Targets In the Eyementioning

confidence: 99%

Section: P2xr Modulators As Drug Targets In the Eyementioning

confidence: 99%

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Ocular Purine Receptors as Drug Targets in the Eye

Civan

2016

Journal of Ocular Pharmacology and Therapeutics

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“…ATP and other nucleotides and adenosine have emerged as important regulators of ocular functions, particularly involved in neuroprotection, intraocular pressure, immunomodulation, vasodilatation, and retinal functioning [8][9][10][11][12]. ATP and other purines are present in vitreous fluids (VFs) and aqueous humor, and their concentrations can be modulated in pathological conditions such as dry eye disease [13], glaucoma [10,14,15], ischemia reperfusion [8], age-related macular degeneration [16], and DR [17].…”

Section: Introductionmentioning

confidence: 99%

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

et al. 2016

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“…Purinergic signaling has been reported to be involved in the degeneration of the injured retina. 30 Based on previous research, purine metabolism was associated with the proliferation of retinal glial cells and demonstrated protective effects on retinal degeneration. The finding of this study provided improved understanding of the role of lncRNAs on AMD development by both phototransduction and purine metabolism.…”

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confidence: 99%

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

Zhu

Xing

et al. 2017

IJN

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Background Age-related macular degeneration (AMD) is one of the most common causes of adult blindness in developed countries. However, the role of long noncoding RNAs (lncRNAs) in the development and progression of early AMD is unclear. Methods We established the lncRNA profile of early AMD by reannotation of microarrays from the gene expression omnibus database. Quantitative real-time polymerase chain reaction was used to determine the expression of selected lncRNAs. Results The expression profiles of 9 cases of AMD and 7 controls were studied. A total of 266 differentially expressed genes (DEGs) were detected (94 upregulated and 172 downregulated). Among all the DEGs, 64 were lncRNAs. Advanced bioinformatics analyses demonstrated that differentially expressed lncRNAs could play significant roles in visual perception, sensory perception of light stimulus, and cognition. The pathway analyses showed that the two most significantly influenced Kyoto Encyclopedia of Genes and Genomes pathways were those of phototransduction and purine metabolism. By the analyses of the key lncRNAs, it was found that RP11-234O6.2 was downregulated in the aging retinal pigment epithelium (RPE) cellular model. Exogenous RP11-234O6.2 treatment led to increased cell viability and improved apoptosis but it did not affect the cell migration ability of aging RPE cells. Conclusion This study indicated that lncRNAs are differentially expressed in early AMD and may produce important regulative effects. An lncRNA, RP11-234O6.2, might be involved in the biological regulation of early AMD and have therapeutic potential.

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Purinergic signaling in retinal degeneration and regeneration

Cited by 65 publications

References 207 publications

Ocular Purine Receptors as Drug Targets in the Eye

Ocular Purine Receptors as Drug Targets in the Eye

Deregulation of ocular nucleotide homeostasis in patients with diabetic retinopathy

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration

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