Effect of SCH442416 on glutamate uptake in retinal Müller cells at increased hydrostatic pressure

Li,Yong; Liu,Xiaohong; Huang,Shouyue; Huang,Ping; Zhong,Yisheng

doi:10.3892/mmr.2015.3882

Effect of SCH442416 on glutamate uptake in retinal Müller cells at increased hydrostatic pressure

Authors:
- Yong Li
- Xiaohong Liu
- Shouyue Huang
- Ping Huang
- Yisheng Zhong
View Affiliations

Affiliations: Department of Ophthalmology, Tongren Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai 200336, P.R. China, Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai 200025, P.R. China, Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai 200025, P.R. China
Published online on: June 3, 2015 https://doi.org/10.3892/mmr.2015.3882
Pages: 3993-3998

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The A2A receptor (A2AR) antagonist has been considered as an attractive option to improve the treatment of neurological disorders, and the function of A2AR antagonist may inhibit the release of glutamate and prevent neuron damage. The aim of the present study was to investigate whether SCH442416 can modulate the glutamate uptake in retinal Müller cells under increased hydrostatic pressure. The levels of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) were assessed in retinal Müller cells under 40 mmHg pressure for 24 h using reverse transcription‑quantitative polymerase chain reaction and western blotting, and a glutamate uptake assay was performed using a scintillation counting method. Following treatment of the Müller cells with 100 nM SCH442416 under 40 mmHg pressure for 24 h, the mRNA and protein expression levels of GS and GLAST, and glutamate uptake activity were investigated. Under 40 mmHg pressure, the expression levels of GS and GLAST in the Müller cells, and glutamate uptake activity were significantly reduced. Treatment with SCH442416 significantly ameliorated the decreased expression levels of GS and GLAST, and improved the glutamate uptake activity in the retinal Müller cells exposed to 40 mmHg pressure, resulting in increased expression levels of GS and GLAST, and increased glutamate uptake activity in the Müller cells under pressure. These results suggested that SCH442416 may be a potential candidate as a beneficial neuroprotective agent for the treatment of glaucoma by accelerating the clearance of extracellular glutamate.

View Figures

View References

1	Foster PJ, Buhrmann R, Quigley HA and Johnson GJ: The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 86:238–242. 2002. View Article : Google Scholar : PubMed/NCBI
2	Kwon YH, Fingert JH, Kuehn MH and Alward WL: Primary open angle glaucoma. N Engl J Med. 360:1113–1124. 2009. View Article : Google Scholar : PubMed/NCBI
3	Quigley HA: Glaucoma. Lancet. 377:1367–1377. 2011. View Article : Google Scholar : PubMed/NCBI
4	Som mer A: Intraocula r pressure and glaucoma. Am J Ophthalmol. 107:186–188. 1989. View Article : Google Scholar
5	Newman E and Reichenbach A: The Müller cell: A functional element of the retina. Trends Neurosci. 19:307–312. 1996. View Article : Google Scholar : PubMed/NCBI
6	Pow DV and Crook DK: Direct immunocytochemical evidence for the transfer of glutamine from glial cells to neurons: Use of specific antibodies directed against the D-steroisomers of glutamate and glutamine. Neuroscience. 70:295–302. 1996. View Article : Google Scholar : PubMed/NCBI
7	Dreyer EB: A proposed role for excitotoxicity in glaucoma. J Glaucoma. 7:62–67. 1998. View Article : Google Scholar : PubMed/NCBI
8	Naskar R, Vorwerk CK and Dreyer EB: Concurrent downregulation of a glutamate transporter and receptor in glaucoma. Invest Ophthamol Vis Sic. 41:1940–1944. 2000.
9	Zhong YS, Leung CK and Pang CP: Glial cells and glaucomatous neuropathy. Chin Med J. 120:326–335. 2007.PubMed/NCBI
10	Kawasaki A, Otori Y and Barnstable CJ: Müller cell pretection of rat retinal ganglion cells from glutamate and nitric oxide neurotoxicity. Invest Ophthamol Vis Sic. 41:3444–3450. 2000.
11	Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN and Linden J: Nomenclature and classification of adenosine receptors. Pharmacol Rev. 53:527–552. 2001.PubMed/NCBI
12	Ghiardi GJ, Gidday JM and Roth S: The purine nucleoside adenosine in retinal ischemia-reperfusion injury. Vision Res. 39:2519–2535. 1999. View Article : Google Scholar : PubMed/NCBI
13	Larsen AK and Osborne NN: Involvement of adenosine in retinal ischemia. Studies on the rat. Invest Ophthalmol Vis Sci. 37:2603–2611. 1996.PubMed/NCBI
14	Li B and Roth S: Retinal ischemic preconditioning in the rat: Requirement for adenosine and repetitive induction. Invest Ophthalmol Vis Sci. 40:1200–1216. 1999.PubMed/NCBI
15	Wang Z, Che PL, Du J, Ha B and Yarema KJ: Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drug candidate ZM241385. PLoS One. 5:e138832010. View Article : Google Scholar : PubMed/NCBI
16	Tarazi FI, Sahli ZT, Wolny M and Mousa SA: Emerging therapies for Parkinson's disease: From bench to bedside. Pharmacol Ther. 144:123–133. 2014. View Article : Google Scholar : PubMed/NCBI
17	Pepponi R, Ferrante A, Ferretti R, et al: Region-specific neuroprotective effect of ZM 241385 towards glutamate uptake inhibition in cultured neurons. Eur J Pharmacol. 617:28–32. 2009. View Article : Google Scholar : PubMed/NCBI
18	Yu J, Zhong Y, Cheng Y, et al: Effect of high hydrostatic pressure on the expression of glutamine synthetase in rat retinal Müller cells cultured in vitro. Exp Ther Med. 2:513–516. 2011.PubMed/NCBI
19	Statement for the Use of Animals in Ophthalmic and Visual Research. The Association for Research in Vision and Ophthalmology; Rockville: 2015
20	Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e452001. View Article : Google Scholar : PubMed/NCBI
21	Goldblum D and Mittag T: Prospects for relevant glaucoma models with retinal GC damage in the rodent eye. Vision Res. 42:471–478. 2002. View Article : Google Scholar : PubMed/NCBI
22	Vizi ES, Kisfali M and Lőrincz T: Role of nonsynaptic GluN2B-containing NMDA receptors in excitotoxicity: evidence that fluoxetine selectively inhibits these receptors and may have neuroprotective effects. Brain Res Bull. 93:32–38. 2013. View Article : Google Scholar
23	Siliprandi R, Canella R, Carmignoto G, Schiavo N, Zanellato A, Zanoni R and Vantini G: N-methyl-D-aspartate-induced neurotoxicity in the adult rat retina. Vis Neurosci. 8:567–573. 1992. View Article : Google Scholar : PubMed/NCBI
24	Dreyer EB, Zurakowski D, Schumer RA, Podos SM and Lipton SA: Elevated glutamate in the vitreous body of humans and monkeys with glaucoma. Arch Ophthalmol. 114:299–305. 1996. View Article : Google Scholar : PubMed/NCBI
25	Dreyer EB and Grosskreutz CL: Excitatory mechanisms in retinal ganglion cell death in primary open angle glaucoma (POAG). Clin Neurosci. 4:270–273. 1997.PubMed/NCBI
26	Vorwerk CK, Gorla MS and Dreyer EB: An experimental basis for implicating excitotoxicity in glaucomatous optic neuropathy. Surv Ophthalmol. 43(Suppl 1): S142–S150. 1999. View Article : Google Scholar : PubMed/NCBI
27	Danbolt NC: Glutamate uptake. Prog Neurobiol. 65:1–105. 2001. View Article : Google Scholar : PubMed/NCBI
28	Naskar R, Vorwerk CK and Dreyer EB: Concurrent downregulation of a glutamate transporter and receptor in glaucoma. Invest Ophthalmol Vis Sci. 41:1940–1944. 2000.PubMed/NCBI
29	Martin KR, Levkovitch-Verbin H, Valenta D, Baumrind L, Pease ME and Quigley HA: Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat. Invest Ophthalmol Vis Sci. 43:2236–2243. 2002.PubMed/NCBI
30	Ishikawa M, Yoshitomi T, Zorumski CF and Izumi Y: Effects of acutely elevated hydrostatic pressure in the rat ex vivo retinal preparation. Invest Ophthalmol Vis Sci. 51:6414–6423. 2010. View Article : Google Scholar : PubMed/NCBI
31	Ishikawa M, Yoshitomi T, Zorumski CF and Izumi Y: Downregulation of glutamine synthetase via GLAST suppression induces retinal axonal swelling in a rat ex vivo hydrostatic pressure model. Invest Ophthalmol Vis Sci. 52:6604–6616. 2011. View Article : Google Scholar : PubMed/NCBI
32	Kvanta A, Seregard S, Sejersen S, Kull B and Fredholm BB: Localization of adenosine receptor messenger RNAs in the rat eye. Exp Eye Res. 65:595–602. 1997. View Article : Google Scholar
33	Blazynsk C: Discrete distributions of adenosine receptors in mammalian retina. J Neurochem. 54:648–655. 1990. View Article : Google Scholar
34	Crooke A, Guzmán-Aranguez A, Peral A, Abdurrahman MK and Pintor J: Nucleotides in ocular secretions: Their role in ocular physiology. Pharmacol Ther. 119:55–73. 2008. View Article : Google Scholar : PubMed/NCBI
35	Li B, Rosenbaum PS, Jennings NM, Maxwell KM and Roth S: Differing roles of adenosine receptor subtypes in retinal ischemia-reperfusion injury in the rat. Exp Eye Res. 68:9–17. 1999. View Article : Google Scholar : PubMed/NCBI
36	Zhong Y, Yang Z, Huang WC and Luo X: Adenosine, adenosine receptors and glaucoma: An updated overview. Biochim Biophys Acta. 1830:2882–2890. 2013. View Article : Google Scholar : PubMed/NCBI