Volume 9, Issue 3 (2018)                   JMBS 2018, 9(3): 325-330 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Ranaei Pirmardan E, Soheili Z, Samiei S, Ahmadieh H, Mowla S, Masoumi M et al . Acute Induction of Ganglion Cell Death and Generation of Mouse Model of Glaucoma by N-Methyl-D-Aspartate. JMBS 2018; 9 (3) :325-330
URL: http://biot.modares.ac.ir/article-22-24339-en.html
1- Molecular Genetics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran
2- Molecular Medicine Department, Medical Biotechnology Institute, National Institute of Genetic Engineering & Biotechnology, Tehran, Iran, National Institute of Genetic Engineering & Biotechnology, Pajoohesh Boulevard, Pajoohesh Township, Kilometer 15, Tehran-Karaj Highway, Tehran, Iran. Postal Code: 1497716316 , soheili@nigeb.ac.ir
3- Blood Transfusion Research Center, High Institute for Research & Education in Transfusion Medicine, Tehran, Iran
4- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5- Molecular Medicine Department, Medical Biotechnology Institute, National Institute of Genetic Engineering & Biotechnology, Tehran, Iran
6- Molecular Medicine Department, Advanced Technologies in Medicine Faculty, Iran University of Medical Sciences, Tehran, Iran
Abstract:   (8230 Views)
Aims: Glaucoma is an optic neuropathy that causes loss of retinal ganglion cells (RGC) and leads to blindness. This disease is a leading cause of blindness worldwide. For pre-clinical studies and finding novel therapies, using functional animal models is unavoidable. One of these models is the mice treated with N-Methyl-D-Aspartate (NMDA). The aim of this study was the acute induction of ganglion cell death and generation of mouse experimental model of glaucoma by N-Methyl-D-Aspartate.
Materials and Methods: In this experimental study, the creation of model mice with NMDA neurotoxin were created. For this purpose, retinal cell damage was induced in vivo in mice by intravitreal injection of NMDA. After removing the eyes, tissue analyses were performed on sample and control eyes. After tissue staining, the number of ganglion cells and the thickness of the retina layers and Ganglion Cell Complex (GCC) were evaluated. In addition, number of ganglion cells, thicknesses of the retina, and GCC of the optic nerve disc were measured in samples.
One-way ANOVA and SPSS 22 software were used to analyze the data.
Findings: Only 3 days after the injection to eye samples of NMDA, the thickness of the GCC and retinal layers as well as the number of ganglion cells significantly decreased compared to the control samples. The 50% reduction in the number of ganglion cells in the glucoma sample was confirmed.
Conclusion: Three days after the injection of NMDA to eye samples, the thickness of the GCC and retinal layers as well as the number of ganglion cells is significantly decreased compared to the control samples.
Full-Text [PDF 577 kb]   (2076 Downloads)    
Subject: Agricultural Biotechnology
Received: 2016/07/1 | Accepted: 2016/08/22 | Published: 2018/09/22

1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-7. [Link] [DOI:10.1136/bjo.2005.081224]
2. Thylefors B, Megrel ADI, Pararajasegaram R, Dadzie KY. Available data on blindness (update 1994). Ophthalmic Epidemiol. 1995;2(1):5-39. [Link] [DOI:10.3109/09286589509071448]
3. ‏3- Bouhenni RA, Dunmire J, Sewell A, Edward DP . Animal models of glaucoma. J Biomed Biotechnol. 2012;2012:1-12. [Link] [DOI:10.1155/2012/692609]
4. Chang B, Hawes NL, Hurd RE, Wang J, Howell D, Davisson MT, et al. Mouse models of ocular diseases. Vis Neurosci. 2005;22(5):587-93. [Link] [DOI:10.1017/S0952523805225075]
5. ‏5- Won J, Ying Shi L, Hicks W, Wang J, Hurd R, Naggert JK, et al. Mouse model resources for vision research. J Ophthalmol. 2011;2011:1-13. [Link] [DOI:10.1155/2011/391384]
6. ‏6- Vecino E. Animal models in the study of the glaucoma: Past, present and future. Arch Soc Esp Oftalmol. 2008;83(9):517-20. [Link]
7. ‏7- Rasmussen CA, Kaufman PL. Primate glaucoma models. J Glaucoma. 2005;14(4):311-‎4. [Link]
8. Dietrich U. Feline glaucomas. Clin Tech Small Anim Pract. 2005;20(2):108-16.‏ [Link] [DOI:10.1053/j.ctsap.2004.12.015]
9. Ruiz-Ederra J, García M, Hernández M, Urcola H, Hernández-Barbáchano E, Araiz J, et al. The pig eye as a novel model of glaucoma. Exp Eye Res. 2005;81(5):561-9. [Link] [DOI:10.1016/j.exer.2005.03.014]
10. Pang IH, Clark AF. Rodent models for glaucoma retinopathy and optic neuropathy. J ‎Glaucoma. 2007;16(5):483-505. [Link] [DOI:10.1097/IJG.0b013e3181405d4f]
11. ‏11- Chang B. Mouse models for studies of retinal degeneration and diseases. Methods Mol Biol. 2013;935:27-39. [Link] [DOI:10.1007/978-1-62703-080-9_2]
12. ‏12- Urcola JH, Hernández M, Vecino E. Three experimental glaucoma models in rats: Comparison of the effects of intraocular pressure elevation on retinal ganglion cell size and death. Exp Eye Res. 2006;83(2):429-37.‏ [Link] [DOI:10.1016/j.exer.2006.01.025]
13. John SW, Smith RS, Savinova OV, Hawes NL, Chang B, Turnbull D, et al. Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Invest Ophthalmol Vis Sci. 1998;39(6):951-62. [Link]
14. ‏14- Maass A, Von Leithner PL, Luong V, Guo L, Salt TE, Fitzke FW, et al. Assessment of rat and mouse RGC apoptosis imaging in vivo with different scanning laser ophthalmoscopes. Curr Eye Res. 2007;32(10):851-61. [Link] [DOI:10.1080/02713680701585872]
15. Li Y, Schlamp CL, Poulsen KP, Nickells RW. Bax-dependent and independent pathways of retinal ganglion cell death induced by different damaging stimuli. Exp Eye Res. 2000;71(2):209-13. [Link] [DOI:10.1006/exer.2000.0873]
16. Seitz R, Tamm ER. N-methyl-D-aspartate (NMDA)-mediated excitotoxic damage: A mouse model of acute retinal ganglion cell damage. Methods Mol Biol. 2013;935:99-109.‏ [Link] [DOI:10.1007/978-1-62703-080-9_7]
17. McKinnon, S.J., C.L. Schlamp, and R.W. Nickells, Mouse models of retinal ganglion cell death and ‎glaucoma. Experimental Eye Res. 2009. 88(4): p. 816-824‎‏.‏ [Link] [DOI:10.1016/j.exer.2008.12.002]
18. ‏18- Vecino E, Sharma SC. Glaucoma animal models. London: Intech Open Access Publisher; 2011. 319-29. [Link]
19. Kaur C, S Foulds W Ling EA. Hypoxia-ischemia and retinal ganglion cell damage. Clin ‎Ophthalmol. 2008;2(4):879-89. [Link]
20. Hernández C, Simó R. Simo. Neuroprotection in diabetic retinopathy. Curr Diab Rep. 2012;12(4):329-‎‎37. [Link]
21. Zhou X, Hollern D, Liao J, Andrechek E, Wang H. NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and ‎extrasynaptic receptors. Cell Death Dis. 2013;4:e560. [Link] [DOI:10.1038/cddis.2013.82]
22. Bai N, Aida T, Yanagisawa M, Katou S, Sakimura K, Mishina M, et al. NMDA receptor subunits have different roles in NMDA-induced neurotoxicity in the retina. ‎Mol Brain. 2013;6:34-42. [Link] [DOI:10.1186/1756-6606-6-34]
23. ‏23- Awai M, Koga T, Inomata Y, Oyadomari S, Gotoh T, Mori M, et al. NMDA-induced retinal injury is mediated by an endoplasmic reticulum stress-related protein, CHOP/GADD153. J Neurochem. 2006;96(1):43-52. [Link] [DOI:10.1111/j.1471-4159.2005.03502.x]
24. Lebrun-Julien F, Duplan L, Pernet V, Osswald I, Sapieha P, Bourgeois P, et al. Excitotoxic death of retinal neurons in vivo occurs via a non-cell-autonomous mechanism. J Neurosci. 2009;29(17):5536-45. [Link] [DOI:10.1523/JNEUROSCI.0831-09.2009]
25. ‏25- Martins RA, Silveira MS, Curado MR, Police AI, Linden R. NMDA receptor activation modulates programmed cell death during early post-natal retinal development: A BDNF-dependent mechanism. J Neurochem. 2005;95(1):244-53. [Link] [DOI:10.1111/j.1471-4159.2005.03360.x]
26. DeParis SW, Caprara C, Grimm C. Intrinsically photosensitive retinal ganglion cells are resistant to N-methyl-D-aspartic acid excitotoxicity. Mol Vis. 2012;18:2814-27. [Link]
27. Nakano N, Ikeda HO, Hangai M, Muraoka Y, Toda Y, Kakizuka A. et al. Longitudinal and simultaneous imaging of retinal ganglion cells and inner retinal layers in a mouse model of glaucoma induced by N-methyl-D-aspartate. Invest Ophthalmol Vis Sci. 2011;52(12):8754-62. [Link] [DOI:10.1167/iovs.10-6654]
28. Shimazawa M, Suemori S, Inokuchi Y, Matsunaga N, Nakajima Y, Oka T, et al. A novel calpain inhibitor, ((1S)-1-((((1S)-1-Benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), reduces murine retinal cell death in vitro and in vivo. J Pharmacol Exp Ther. 2010;332(2):380-7. [Link] [DOI:10.1124/jpet.109.156612]
29. Fischer MD, Huber G, Beck SC, Tanimoto N, Muehlfriedel R, Fahl E, et al. Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography. PLoS One. 2009;4(10):e7507. [Link] [DOI:10.1371/journal.pone.0007507]
30. Ohno Y, Makita S, Shimazawa M, Tsuruma K, Yasuno Y, Hara H. Thickness mapping of the inner retina by spectral-domain optical coherence tomography in an N-methyl-D-aspartate-induced retinal damage model. Exp Eye Res. 2013;113:19-25. [Link] [DOI:10.1016/j.exer.2013.05.009]
31. Dysli C, Enzmann V, Sznitman R, Zinkernagel MS. Quantitative analysis of mouse retinal layers using automated segmentation of spectral domain optical coherence tomography images. Transl Vis Sci Technol. 2015;4(4):9. [Link] [DOI:10.1167/tvst.4.4.9]
32. Karl MO, Hayes S, Nelson BR, Tan K, Buckingham B, Reh TA. Stimulation of neural regeneration in the mouse retina. Proc Natl Acad Sci U S A. 2008;105(49):19508-13. [Link] [DOI:10.1073/pnas.0807453105]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.