Mechanisms for Increased Resistance to Aqueous Humor Outflow in Glucocorticoid-induced Glaucoma_West China Medical Journal

Authors：

1Department of Ophthalmology,2nd Affiliated Hospital,Nanhua University;2Department of Ophthalmology and Ophthalmic Laboratories,West China Hospital,Sichuan University,Chengdu 610041,China;3Tongren Ophthalmic Center,Capital University of Medical Sciences;

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Keywords：

青光眼; 糖皮质激素; myocilin/TIGR蛋白; 纤连蛋白; 肌动蛋白交联网; 血清淀粉样物质A

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目的：本研究通过观察经地塞米松处理前后培养的人小梁细胞的变化,探讨激素性青光眼房水排出阻力增加的机制。方法：将人类小梁细胞培养至接近体内的高分化状态，用地塞米松处理后,观察细胞形态的变化，并检测以下蛋白的分布和表达：(1)myocilin/TIGR蛋白；(2)纤连蛋白；(3)肌动蛋白交联网的形成；(4)血清淀粉样物质A蛋白。结果：人小梁细胞经地塞米松处理后(1)胞体变大，排列不规则，边界模糊，呈“融合”状；(2)细胞内外myocilin/TIGR蛋白表达均明显增加，其胞外表达与纤连蛋白位置一致,提示相互作用；(3)纤连蛋白表达增加；(4)CLANs形成，细胞间连接增强；(5)血清淀粉样物质A蛋白表达增加。结论：人类小梁细胞经地塞米松处理后形态发生变化，可能与应力纤维变化及myocilin蛋白在细胞内积聚有关。细胞间边界不清，与细胞外基质蛋白过度表达、沉积有关。小梁细胞外基质沉积以及异常的细胞间连接等改变与房水排出阻力增加的病理过程有关。

Citation： TAN Juan,CAO Guiqun,GUO Lin,et al.. Mechanisms for Increased Resistance to Aqueous Humor Outflow in Glucocorticoid-induced Glaucoma. West China Medical Journal, 2008, 23(1): 67-69. doi: Copy

1.
2.	eshwork cells[J].Invest Ophthalmol Vis Sci,1994,35(1):281-94.
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14.	Zhou Z，Vollrath D．A cellular assay distinguishes normal and mutant TIGR／myocilin protein[J].Hum Mol Genet，1999，8(12):2221-2228.
15.	Rozsa FW，Shimlzu S，Lichter PR，Johnson AT.Othman MI.Scott K，et a1.GLCIA mutations point to regions of potential functional importance on the TIGR/MYOC protein[J].Mol Vis,1998,4:20.
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17.	Dickerson JE Jr,Steely HT Jr,English-Wright SL,et al.The effect of dexamethasone on integrin and laminin expression in cultured human trabecular meshwork cells[J].Exp Eye Res,1998,66:731-738.
18.	Kaufman PL,Erickson KA.Cytochalasin B and D dose-outflow facility response relationships in the cynomolgus monkey[J].Invest Ophthalmol Vis Sci,1982,23:646-650.
19.	Liu X,Cai S,Glasser A,Volberg T,Polansky JR,Fauss DJ,Geiger B,Kaufman PL.Effect of H-7 on cultured human trabecular meshwork cells[J].Molecular Vision,2001,7:145-153.
20.	Clark AF,Wilson K,McCartney MD,Miggans ST,Kunkle M,Howe W.Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular m.

1.
2. eshwork cells[J].Invest Ophthalmol Vis Sci,1994,35(1):281-94.
3. [13]Gotlieb AI.The endothelial cytoskeleton:organization in normal and regenerating endothelium[J].Toxicol Pathol,1990,18(4 Pt 1):603-17.
4. [14]Clark AF,Brotchie D,Read AT,Hellberg P,English-Wright S,Pang IH,Ethier CR,Grierson I.Dexamethasone alters F-actin architecture and promotes cross-linkedactin network formation in human trabecular meshwork tissue[J].Cell Motil Cytoskeleton,2005,60(2):83-95.
5. [15]Clark AF,Wilson K,McCartney MD,et al.Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells[J].Invest Ophthalmol Vis Sci,1994,35:281-294.
6. [16]Clark AF,Lane D,Wilson K,et al.Inhibition of dexamethasone-induced cytoskeletal changes in cultured human trabecular meshwork cells by tetrahydrocortisol[J].Invest Ophthalmol Vis Sci,1996,37(5):805-813.
7. [17]Matsumoto Y,Johnson DH.Dexamethasone decreases phagocytosis by human trabecular meshwork cells in situ[J].Invest Ophthalmol Vis Sci,1997,38(9):1902-1907.
8. [18]El Kebie,Jozsef L,Khreiss T,et al.Aspirin-triggered lipoxins override the apoptosis-delaying action of serum amyloid A in human neutrophils:a novel mechanism for resolution of inflammation[J].J Immunol,2007,179(1):616-22.
9. Bill A.Mechanisms and routes of aqueous humor drainage.In:Albert DM,Jakobiec FA,eds.Principles and practice of ophthalmology:basic sciences[M].Philadelphia:Saunders,1994：206-226.
10. Fine BS,Yanoff M,Stone RA.A clinicopathologic study of four cases of primary open-angle glaucoma compared to normal eyes[J].Am J Ophthalmol,1981：91:88-105.
11. Rohen JW.Why is intraocular pressure elevated in chronic simple glaucoma[J]?Ophthalmology,1983,90:758-765.
12. Alvarado J,Murphy C,Polansky J,et al.Age-related changes in trabecular meshwork cellularity[J].Invest Ophthalmol Vis Sci,1981,21:714-727.
13. Polansky JR,Alvarado JA.Cellular mechanisms influencing the aqueous humor outflow pathway.In:Albert DM,Jakobiec FA,eds.Principles and practice of ophthalmology:basic sciences[M].Philadelphia:Saunders,1994：226-251.
14. Zhou Z，Vollrath D．A cellular assay distinguishes normal and mutant TIGR／myocilin protein[J].Hum Mol Genet，1999，8(12):2221-2228.
15. Rozsa FW，Shimlzu S，Lichter PR，Johnson AT.Othman MI.Scott K，et a1.GLCIA mutations point to regions of potential functional importance on the TIGR/MYOC protein[J].Mol Vis,1998,4:20.
16. Steely HT，Browder SL,Julian MB,et al.The effects of dexamethasone on fibronectin expression in cultured human trabecular meshwork cells[J].Invest Ophthalmol Vis Sci,1992,33:2242-2250.
17. Dickerson JE Jr,Steely HT Jr,English-Wright SL,et al.The effect of dexamethasone on integrin and laminin expression in cultured human trabecular meshwork cells[J].Exp Eye Res,1998,66:731-738.
18. Kaufman PL,Erickson KA.Cytochalasin B and D dose-outflow facility response relationships in the cynomolgus monkey[J].Invest Ophthalmol Vis Sci,1982,23:646-650.
19. Liu X,Cai S,Glasser A,Volberg T,Polansky JR,Fauss DJ,Geiger B,Kaufman PL.Effect of H-7 on cultured human trabecular meshwork cells[J].Molecular Vision,2001,7:145-153.
20. Clark AF,Wilson K,McCartney MD,Miggans ST,Kunkle M,Howe W.Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular m.

West China Medical Journal

Mechanisms for Increased Resistance to Aqueous Humor Outflow in Glucocorticoid-induced Glaucoma

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