|
2.2 DR时Muller细胞生理变化
糖尿病视网膜Muller细胞谷氨酸转运蛋白功能障碍，GS的活性和含量明显降低，导致Muller细胞将细胞外间隙的谷氨酸转运到细胞内的能力下降。通过动物实验研究发现，4WSTZ大鼠视网膜Muller细胞谷氨酸转运蛋白功能已发生变化，13W时谷氨酸转运蛋白功能下降了67％，并且谷氨酸转运蛋白功能变化早于GS活性的降低［16］。突触间隙过高浓度的谷氨酸过度刺激离子型谷氨酸受体(NMDA)，引起视网膜细胞的细胞膜钙离子通道开放，导致细胞内钙离子超载［17］。细胞内增加的钙离子充当第二信使启动级联反应导致视网膜细胞死亡，对视网膜具有兴奋毒性作用。在糖尿病患者视网膜血管病变之前，其视觉敏感度及色觉敏感度下降，并且视网膜振荡电位b波异常。这说明神经细胞的变性早于在血管病变。最近的研究［18］体内高血糖能明显降低视网膜神经细胞GluR1 and GluR6/7亚单位的蛋白含量，提高GluR2 and KA2亚单位含量，同时神经细胞Ca2+稳态破坏，这可能是早期糖尿病患者视敏度受损的原因。
人类视网膜Muller细胞表达P2X7受体，Bringmann A, Pannicke T等通过一系列的研究［19，20，21］表明, PDR时Muller 细胞P2X7受体增加, 细胞外ATP与受体结合,引起细胞内储存的Ca2+释放和细胞外Ca2+内流。Ca2+内流激活钙依赖的钾通道开放, 内向整合K1＋通道（Kir）电流明显降低,膜去极化,电压门控的钠离子电流增加。Muller细胞内离子的变化影响了其对细胞外局部离子浓度的调控和神经递质的摄取。细胞外Ca2+内流和Ca2+激活的钾通道可能促进Muller细胞增殖，参与PDR的发生与发展。
综上所述，糖尿病早期视网膜Muller细胞的超微结构和生理功能已发生变化，并且这种结构及功能的异常不仅影响早期糖尿病患者神经细胞功能异常（表现为视觉敏感度及色觉敏感度下降，视网膜振荡电位b波异常），而且影响整个DR的进展过程。因此用定量分析的方法深入探讨Muller细胞在DR发生发展中的作用及机制，延缓或逆转其结构及功能异常成为预防与治疗DR的热点，并且已经有学者提出通过移植Muller细胞来治疗DR的建议。
【参考文献】
［1］Malone J I, Morrison A D, Pavan P R, et al. Prevalence and significance of retinopathy in subjects with type 1 diabetes of less than 5 years duration screened for the diabetes control and complications trial Diabetes Care ［J］. 2001, 24(3):522-526.
［2］Nakajima M, Cooney M J, Tu A H, et al. Normalization of retinal vascular permeability in experimental diabetes with genistein ［J］. Invest Ophthalmol Vis Sci.2001, 42(9):2110-2114.
［3］Rasmussen K E. A Morphometric Study of the Muller Cell Cytoplasm in the Rat Retina ［J］.Ultrastructure Research, 1972,39:413-427.
［4］李凤鸣 主编.中华眼科学（上册）［M］.北京：人民卫生出版社 2005：114-115.
［5］成令忠 主编.现代组织学（第1版）［M］.上海：科学技术文献出版社 2003：488-491.
［6］RASMUSSEN K E. A Morphometric Study of the Muller Cell,Their Nuclei and Mitochodria Rat Retina ［J］. Ultrastructure Research, 1973，44：96-112.
［7］Du J L,Xu L Y，Yang X L.Glycine receptor and transporters on bull frog retinal muller cells［J］. Neuroreport, 2002,13(13):1653-1656.
［8］Newman E A. A purinergic dialogue between glia and neurons in the retina Novartis Found Symp. 2006, 276:193-202.
［9］Li Q, Zemel E, Miller B,et al. Early retinal damage in experimental diabetes: electroretinographical and morphological observations［J］.Exp Eye Res,2002, 74(5):615-625.
［10］Amin R H, Frank R N, Kennedy A, et al.Vascular endothelial growth factor is present in glial cells of the retina and optic nerve of human subjects with nonproliferative diabetic retinopathy ［J］. Invest Ophthalmol Vis Sci, 1997, 38(1):36-47.
［11］Esguerra M. Miller RF CD38 expression and NAD+-induced intracellular Ca+ mobilization in isolated retinal［J］. Muller cells Glia, 2002,39(3):314-319 .
［12］Newman E A. Propagation of intercellular calcium waves in retinal astrocytes and Muller cells ［J］. Neurosci, 2001,21(7): 2215-2223.
［13］Schellini S A, Gregorio E A, Spadella C T, et al.Muller cells and diabetic retinopathy Braz［J］. Med Biol Res, 1995, 28(9):977-980.
［14］凌志红，徐格致，等.糖尿病视网膜Muller细胞病理改变的体内外研究［J］.眼科研究,2005,23(3):262-265.
［15］Bek T. Immunohistochemical characterization of retinal glial cell changes in areas of vascular occlusion secondary to diabetic retinopathy［J］. Acta Ophthalmol Scand, 1997, 75(4):388-392.
［16］Guidry C. The role of Muller cells in fibrocontractive retinal disorders ［J］. Prog Reti Eye Res, 2005, 24:75-86.
［17］Li Q，Puro D G. DiabetesInduced Dysfunction of the Glutamate Transporter in Retinal Müller Cells ［J］. Invest Ophthalmol Vis Sci, 2002,43(9):3109-3116.
［18］Erich Lieth, Alistair J. Barber, Baiyang Xu, et al. Glial Reactivity and Impaired Glutamate Metabolism in ShortTerm Experimental Diabetic Retinopathy Diabetes, 1998,47(5):815-820.
［19］Santiago A R, Rosa S C, Santos P F,et al. Elevated glucose changes the expression of ionotropic glutamate receptors subunits and impairs calcium homeostasis in retinal neural cells ［J］. Invest Ophthalmol Vis Sci, 2006,47(9):4130-4137.
［20］Thomas Pannicke,Wolfgang Fischer, Bernd Biedermann,et al. P2X7 Receptors in Muller Glial Cells from the Human Retina［J］. Neurosci, 2000,20(16):5965-5972.
［21］Bringmann A, Pannicke T, Moll V,et al. Upregulation of P2X7 receptor currents in Muller glial cells during proliferative vitreoretinopathy ［J］. Invest Ophthalmol Vis Sci, 2001, 42(3):860-867.
［22］Bringmann A, Pannicke T, Uhlmann S, et al.Membrane conductance of Muller glial cells in proliferative diabetic retinopathy Can ［J］. Ophthalmol, 2002,37(4):221-227.
上一页 [1] [2] |
