Müller细胞生理功能及其在糖尿病视网膜病变中的变化_Chinese Journal of Ocular Fundus Diseases

Authors：

王帅 ,  吴强

;

Corresponding author：

吴强, Email: wyan559@hotmail.com

Keywords：

糖尿病视网膜病变/病因学; 小神经胶质细胞/生理学; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2014.02.029

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Müller细胞接触并包裹视网膜神经元细胞体和突触, 对视网膜神经元的功能及代谢起到支持作用; 对维护视网膜细胞外环境的稳定, 如离子、水平衡和血视网膜屏障(BRB)等具有重要调控作用; 可释放神经胶质递质和刺激性神经物质, 通过对神经递质的再吸收循环, 为视网膜神经元提供神经递质前体进而影响神经突触的活性。此外, Müller细胞对病理刺激能够产生反应。该反应一方面具有视网膜神经元保护作用, 如分泌神经营养因子、吸收降解兴奋性毒素、分泌抗氧化剂等, 另一方面也可引起视网膜神经元谷氨酸盐代谢紊乱和离子平衡紊乱, 导致视网膜水肿和神经元变性损伤。Müller细胞对糖尿病视网膜病变(DR)的发生发展具有重要影响。DR可引起Müller细胞增生, 除造成谷氨酸盐代谢紊乱外, 还会引起Müller细胞大量分泌炎症介质和血管内皮生长因子等破坏BRB。深入研究Müller细胞, 对探讨DR的发病及防治具有重要意义。针对Müller细胞靶向转染的腺病毒载体研制成功, 利用两亲肽携带蛋白或抗体直接转染细胞达到抑制DR的效果, 这些方法为早期防治DR提供了新的途径。

Citation： 王帅, 吴强. Müller细胞生理功能及其在糖尿病视网膜病变中的变化. Chinese Journal of Ocular Fundus Diseases, 2014, 30(2): 219-223. doi: 10.3760/cma.j.issn.1005-1015.2014.02.029 Copy

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9.	Matsui K, Hosoi N, Tachibana M. Active role of glutamate uptake in the synaptic transmission from retinal nonspiking neurons[J]. J Neurosci, 1999, 19:6755-6766.
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1. Reichenbach A, Wurm A, Pannicke T, et al. Müller cells as players in retinal degeneration and edema[J]. Graefe's Arch Clin Exp Ophthalmol, 2007, 245:627-636.
2. Bringmann A, Pannicke T, Biedermann B, et al. Role of retinal glial cells in neurotransmitter uptake and metabolism[J]. Neurochem Int, 2009, 54:143-160.
3. Bringmann A, Iandiev I, Pannicke T, et al. Cellular signaling and factors involved in Müller cell gliosis:neuroprotective and detrimental effects[J]. Prog Retin Eye Res, 2009, 28:423-451.
4. Bringmann A, Pannicke T, Grosche J, et al. Müller cells in the healthy and diseased retina[J]. Prog Retin Eye Res, 2006, 25:397-424.
5. Fletcher EL, Phipps JA, Wilkinson-Berka JL. Dysfunction of retinal neurons and glia during diabetes[J]. Clin Exp Optom, 2005, 88:132-145.
6. Coorey NJ, Shen WY, Chung SH, et al. The role of glia in retinal vascular disease[J]. Clin Exp Optom, 2012, 95:266-281.
7. Derouiche A, Rauen T. Coincidence of L-glutamate/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia:evidence for coupling of GLAST and GS in transmitter clearance[J]. J Neurosci Res, 1995, 42:131-143.
8. Harada T, Harada C, Watanabe M, et al. Functions of the two glutamate transporters GLAST and GLT-1 in the retina[J]. Proc Natl Acad Sci USA, 1998, 95:4663-4666.
9. Matsui K, Hosoi N, Tachibana M. Active role of glutamate uptake in the synaptic transmission from retinal nonspiking neurons[J]. J Neurosci, 1999, 19:6755-6766.
10. Barbour B, Brew H, Attwell D. Electrogenic uptake of glutamate and aspartate into glial cells isolated from the salamander (Ambystoma) retina[J]. J Physiol, 1991, 436:169-193.
11. Barnett NL, Pow DV. Antisense knockdown of GLAST, a glial glutamate transporter, compromises retinal function[J]. Invest Ophthalmol Vis Sci, 2000, 41:585-591.
12. Linser P, Moscona AA. Induction of glutamine synthetase in embryonic neural retina:localization in Müller fibers and dependence on cell interactions[J]. Proc Natl Acad Sci USA, 1979, 76:6476-6480.
13. Biedermann B, Bringmann A, Reichenbach A. High-affinity GABA uptake in retinal glial (Müller) cells of the guinea pig:electrophysiological characterization, immunohistochemical localization, and modeling of efficiency[J]. Glia, 2002, 39:217-228.
14. Pow DV, Crook DK. Direct immunocytochemical evidence for the transfer of glutamine from glial cells to neurons:use of specific antibodies directed against the d-stereoisomers of glutamate and glutamine[J]. Neuroscience, 1996, 70:295-302.
15. Newman E, Reichenbach A. The Müller cell:a functional element of the retina[J]. Trends Neurosci, 1996, 19:307-312.
16. Kofuji P, Biedermann B, Siddharthan V, et al. Kir potassium channel subunit expression in retinal glial cells:implications for spatial potassium buffering[J]. Glia, 2002, 39:292-303.
17. Skatchkov SN, Eaton MJ, Shuba YM, et al. Tandem-pore domain potassium channels are functionally expressed in retinal (Müller) glial cells[J]. Glia, 2006, 53:266-276.
18. Bringmann A, Faude F, Reichenbach A. Mammalian retinal glial (Müller) cells express large-conductance Ca²⁺-activated K⁺ channels that are modulated by Mg²⁺ and pH and activated by protein kinase A[J]. Glia, 1997, 19:311-323.
19. Orkand RK. Glial-interstitial fluid exchange[J]. Ann N Y Acad Sci, 1986, 481:269-272.
20. Karwoski CJ, Lu HK, Newman EA. Spatial buffering of light-evoked potassium increases by retinal Müller (glial) cells[J]. Science, 1989, 244:578-580.
21. Newman EA, Frambach DA, Odette LL. Control of extracellular potassium levels by retinal glial cell K⁺ siphoning[J]. Science, 1984, 225:1174-1175.
22. Reichenbach A, Henke A, Eberhardt W, et al. K⁺ ion regulation in retina[J]. Can J Physiol Pharmacol, 1992, 70 Suppl:S239-247.
23. Marmor MF. Mechanisms of fluid accumulation in retinal edema[J]. Doc Ophthalmol, 1999, 97:239-249.
24. Bringmann A, Reichenbach A, Wiedemann P. Pathomechanisms of cystoid macular edema[J]. Ophthalmic Res, 2004, 36:241-249.
25. Nagelhus EA, Horio Y, Inanobe A, et al. Immunogold evidence suggests that coupling of K⁺ siphoning and water transport in rat retinal Müller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains[J]. Glia, 1999, 26:47-54.
26. Li J, Patil RV, Verkman AS. Mildly abnormal retinal function in transgenic mice without Müller cell aquaporin-4 water channels[J]. Invest Ophthalmol Vis Sci, 2002, 43:573-579.
27. Da T, Verkman AS. Aquaporin-4 gene disruption in mice protects against impaired retinal function and cell death after ischemia[J]. Invest Ophthalmol Vis Sci, 2004, 45:4477-4483.
28. Bringmann A, Uckermann O, Pannicke T, et al. Neuronal versus glial cell swelling in the ischaemic retina[J]. Acta Ophthalmol Scand, 2005, 83:528-538.
29. Wang JJ, Xu XL, Elliott MH, et al. Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage[J]. Diabetes, 2010, 59:2297-2305.
30. Ye XF, Ren H, Zhang M, et al. ERK1/2 signaling pathway in the release of VEGF from Müller cells in diabetes[J]. Invest Ophthalmol Vis Sci, 2012, 53:3481-3489.
31. Yong PH, Zong HL, Medina RJ, et al. Evidence supporting a role for Nε^-(3-formyl-3, 4-dehydropiperidino)lysine accumulation in Müller glia dysfunction and death in diabetic retinopathy[J]. Mol Vis, 2010, 16:2524-2538.
32. Zong H, Ward M, Madden A, et al. Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE)[J]. Diabetologia, 2010, 53:2656-2666.
33. Zhong YM, Li JM, Chen YM, et al. Activation of endoplasmic reticulum stress by hyperglycemia is essential for Müller cell-derived inflammatory cytokine production in diabetes[J]. Diabetes, 2012, 61:492-504.
34. Antonetti DA, Barber AJ, Hollinger LA, et al. Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1:a potential mechanism for vascular permeability in diabetic retinopathy and tumors[J]. J Biol Chem, 1999, 274:23463-23467.
35. Titchenell PM, Lin CM, Keil JM, et al. Novel atypical PKC inhibitors prevent vascular endothelial growth factor-induced blood-retinal barrier dysfunction[J]. Biochem J, 2012, 446:455-467.
36. Huang H, Gandhi JK, Zhong XF, et al. TNFα is required for late BRB breakdown in diabetic retinopathy, and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis[J]. Invest Ophthalmol Vis Sci, 2011, 52:1336-1344.
37. El-Remessy AB, Al-Shabrawey M, Khalifa Y, et al. Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes[J]. Am J Pathol, 2006, 168:235-244.
38. Demircan N, Safran BG, Soylu M, et al. Determination of vitreous interleukin-1(IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy[J]. Eye (Lond), 2006, 20:1366-1369.
39. Aveleira CA, Lin CM, Abcouwer SF, et al. TNF-αsignals through PKCζ/NF-κB to alter the tight junction complex and increase retinal endothelial cell permeability[J]. Diabetes, 2010, 59:2872-2882.
40. Shen X, Zhong YS, Xie B, et al. Pigment epithelium derived factor as an anti-inflammatory factor against decrease of glutamine synthetase expression in retinal Müller cells under high glucose conditions[J]. Graefe's Arch Clin Exp Ophthalmol, 2010, 248:1127-1136.
41. Derevjanik NL, Vinores SA, Xiao WH, et al. Quantitative assessment of the integrity of the blood-retinal barrier in mice[J]. Invest Ophthalmol Vis Sci, 2002, 43:2462-2467.
42. Wang LL, Chen H, Huang K, et al. Elevated histone acetylations in Müller cells contribute to inflammation:a novel inhibitory effect of minocycline[J]. Glia, 2012, 60:1896-1905.
43. Ali TK, Al-Gayyar MM, Matragoon S, et al. Diabetes-induced peroxynitrite impairs the balance of pro-nerve growth factor and nerve growth factor, and causes neurovascular injury[J]. Diabetologia, 2011, 54:657-668.
44. Wurm A, Iandiev I, Hollborn M, et al. Purinergic receptor activation inhibits osmotic glial cell swelling in the diabetic rat retina[J]. Exp Eye Res, 2008, 87:385-393.
45. Pannicke T, Iandiev I, Wurm A, et al. Diabetes alters osmotic swelling characteristics and membrane conductance of glial cells in rat retina[J]. Diabetes, 2006, 55:633-639.
46. Curtis TM, Hamilton R, Yong PH, et al. Müller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products[J]. Diabetologia, 2011, 54:690-698.
47. Owada S, Larsson O, Arkhammar P, et al. Glucose decreases Na⁺, K⁺-ATPase activity in pancreatic β-cells:an effect mediated via Ca²⁺-independent phospholipase A2 and protein kinase C-dependent phosphorylation of the α-subunit[J]. J Biol Chem, 1999, 274:2000-2008.
48. Bringmann A, Skatchkov SN, Biedermann B, et al. Alterations of potassium channel activity in retinal Müller glial cells induced by arachidonic acid[J]. Neuroscience, 1998, 86:1291-1306.
49. Krügel K, Wurm A, Pannicke T, et al. Involvement of oxidative stress and mitochondrial dysfunction in the osmotic swelling of retinal glial cells from diabetic rats[J]. Exp Eye Res, 2011, 92:87-93.
50. L ffler S, Wurm A, Kutzera F, et al. Serum albumin induces osmotic swelling of rat retinal glial cells[J]. Brain Res, 2010, 1317:268-276.
51. Ishikawa M. Abnormalities in glutamate metabolism and excitotoxicity in the retinal diseases[J/OL]. Scientifica (Cairo), 2013, 2013:528940[2014-03-13]. http://www.hindawi.com/journals/scientifica/2013/528940/.
52. Cheung W, Guo L, Cordeiro MF. Neuroprotection in glaucoma:drug-based approaches[J]. Optom Vis Sci, 2008, 85:406-416.
53. Li Q, Puro DG. Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells[J]. Invest Ophthalmol Vis Sci, 2002, 43:3109-3116.
54. Zeng KH, Xu HX, Chen K, et al. Effects of taurine on glutamate uptake and degradation in Müller cells under diabetic conditions via antioxidant mechanism[J]. Mol Cell Neurosci, 2010, 45:192-199.
55. Zeng KH, Xu HX, Mi MT, et al. Dietary taurine supplementation prevents glial alterations in retina of diabetic rats[J]. Neurochem Res, 2009, 34:244-254.
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Chinese Journal of Ocular Fundus Diseases

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