Activation of Muscarinic Receptors Protects against Retinal Neurons Damage and Optic Nerve Degeneration <i>In Vitro</i> and <i>In Vivo</i> Models

Tan, Panpan; Yuan, Haihong; Zhu, Xu; Cui, Yong-Yao; Li, Hui; Feng, Xiao; Qiu, Yu; Chen, Hongzhuan; Zhou, Wei

doi:10.1111/cns.12187

Cited by 32 publications

(26 citation statements)

References 31 publications

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“…76 Pilocarpine also reduced retinal I/R damage caused by elevated IOP in vivo in experimental rats. 77 This neuroprotective effect seems to be mediated via muscarinic M1 receptors, as activation of these receptors leads to upregulation of NF-E2-related factor-2 (Nrf2), which is the key transcription factor of redox homeostasis resulting in upregulation of oxidant defense genes. 78 Pilocarpine significantly increased pulsatile ocular blood flow in patients with untreated OHT in one study.…”

Section: Topical Therapiesmentioning

confidence: 99%

Pharmacotherapy of Glaucoma

Schmidl

Schmetterer²,

Garhöfer³

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

136

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Glaucoma is a group of diseases involving the optic nerve and associated structures, which is characterized by progressive visual field loss and typical changes of the optic nerve head (ONH). The only known treatment of the disease is reduction of intraocular pressure (IOP), which has been shown to reduce glaucoma progression in a variety of large-scale clinical trials. Nowadays, a relatively wide array of topical antiglaucoma drugs is available, including prostaglandin analogues, carbonic anhydrase inhibitors, beta-receptor antagonists, adrenergic agonists, and parasympathomimetics. In clinical routine, this allows for individualized treatment taking risk factors, efficacy, and safety into account. A major challenge is related to adherence to therapy. Sustained release devices may help minimize this problem but are not yet available for clinical routine use. Another hope arises from non-IOP-related treatment concepts. In recent years, much knowledge has been gained regarding the molecular mechanisms that underlie the disease process in glaucoma. This also strengthens the hope that glaucoma therapy beyond IOP lowering will become available. Implementing this concept with clinical trials remains, however, a challenge.

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Section: Topical Therapiesmentioning

confidence: 99%

Pharmacotherapy of Glaucoma

Schmidl

Schmetterer²,

Garhöfer³

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

136

View full text Add to dashboard Cite

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“…Pretreatment of pilocarpine to a rat retinal cell culture attenuated glutamate-induced neurotoxicity, a finding from Tan et al 53 that was dose-dependent and eliminated by application of atropine and pirenzepine, nonselective and M1-selective muscarinic receptor antagonists, respectively. In their in vivo rat model, inner retinal degeneration was significantly reduced by the application of topical 2% pilocarpine, and a cholinergic cell marker ChAT was found to be upregulated.…”

Section: Introductionmentioning

confidence: 86%

“…Authors highlight the potential neuroprotective action of pilocarpine and posit that muscarinic receptors are potential therapeutic targets in glaucoma that might afford a neuroprotective effect. 53 …”

Section: Introductionmentioning

confidence: 99%

One Year of Glaucoma Research in Review—2013 to 2014

Tassel

Radcliffe

Demetriades³

2015

Asia-Pacific Journal of Ophthalmology

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Purpose The purpose of this study was to provide the practicing clinical ophthalmologist with an update of relevant glaucoma literature published from 2013 to 2014. Design Literature review. Methods The authors conducted a 1-year (October 1, 2013, to September 30, 2014) English-language glaucoma literature search on PubMed of articles containing “glaucoma” or “glaucomatous” with title/abstract as a filter. Medical Subject Headings (MeSH) filtered searching was not performed because of the newness of the reviewed material. Results Literature review yielded 2,314 articles, after which we excluded reviews and letters to the editor. We highlighted articles featuring new or updated approaches to the pathophysiology, diagnosis, or treatment of glaucoma and gave preference to human research. Conclusions This review features literature that is of interest to ophthalmologists in practice and also highlights studies that may provide insight to future developments applicable to clinical ophthalmology.

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“…In the visual system, the activation of muscarinic receptors inhibited the damage of retinal neurons submitted to ischemia/reperfusion insults and attenuated the glutamate-induced cytotoxicity in retinal ganglion cells (Tan et al 2013). For this reason, it is important to elucidate the mechanisms concerning the expression of muscarinic receptors in the retinal tissue.…”

Section: Cell Mol Neurobiolmentioning

confidence: 99%

IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

et al. 2015

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Interleukin-4 (IL-4) is a pleiotropic cytokine that regulates several phenomena, among them survival and differentiation of neuronal and glial cells. The aim of this work was to investigate the effect of IL-4 on the cholinergic differentiation of neonatal rat retinal cells in vitro, evaluating its effect on the levels of cholinergic markers (CHT1-high-affinity choline transporter; VAChT-vesicular acetylcholine transporter, ChAT-choline acetyltransferase, AChE-acetylcholinesterase), muscarinic receptors, and on the signaling pathways involved. Lister Hooded rat pups were used in postnatal days 0-2 (P0-P2). Our results show that IL-4 treatment (50 U/mL) for 48 h increases the levels of the cholinergic transporters VAChT and CHT1, the acetylcholinesterase activity, and the number of ChAT-positive cells. It also induces changes in muscarinic receptor levels, leading to a small decrease in M1 levels and a significant increase in M3 and M5 levels after 48 h of treatment. We also showed that IL-4 effect on M3 receptors is dependent on type I IL-4 receptor and on an increase in NFκB phosphorylation. These results indicate that IL-4 stimulates cholinergic differentiation of retinal cells.

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Activation of Muscarinic Receptors Protects against Retinal Neurons Damage and Optic Nerve Degeneration In Vitro and In Vivo Models

Cited by 32 publications

References 31 publications

Pharmacotherapy of Glaucoma

Pharmacotherapy of Glaucoma

One Year of Glaucoma Research in Review—2013 to 2014

IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

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