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中华眼科医学杂志(电子版)

中华眼科医学杂志(电子版) ›› 2021, Vol. 11 ›› Issue (03) : 188 -192. doi: 10.3877/cma.j.issn.2095-2007.2021.03.011

综述

青光眼滤过术后瘢痕化机制与抗瘢痕化治疗的研究进展
马铭绅1, 申颖2, 李文萱3, 关文英2, 康欣4, 赵海霞2,†()   
  1. 1. 010050　呼和浩特，内蒙古医科大学2019级硕士研究生；010050　呼和浩特，内蒙古医科大学附属医院眼科
    2. 010050　呼和浩特，内蒙古医科大学2019级硕士研究生
    3. 010050　呼和浩特，内蒙古医科大学附属医院眼科
    4. 100853　北京，中国人民解放军总医院眼科学部
  • 收稿日期:2020-10-30 出版日期:2021-06-28
  • 通信作者: 赵海霞
  • 基金资助:
    内蒙古自治区自然科学基金项目(2019MS08142)

Advances on the mechanism of glaucoma filtration surgery scarring and anti-scarring treatment

Mingshen Ma1, Ying Shen2, Wenxuan Li3, Wenying Guan2, Xin Kang4, Haixia Zhao2,†()   

  1. 1. Master′s degree 2019, Inner Mongolia Medical University, Hohhot 010050, China; Department of Ophthalmology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
    2. Master′s degree 2019, Inner Mongolia Medical University, Hohhot 010050, China
    3. Department of Ophthalmology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
    4. Department of Ophthalmology, Chinese People′s Liberation Army General Hospital, Beijing 100853, China
  • Received:2020-10-30 Published:2021-06-28
  • Corresponding author: Haixia Zhao
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引用本文：

马铭绅, 申颖, 李文萱, 关文英, 康欣, 赵海霞. 青光眼滤过术后瘢痕化机制与抗瘢痕化治疗的研究进展[J]. 中华眼科医学杂志(电子版), 2021, 11(03): 188-192.

Mingshen Ma, Ying Shen, Wenxuan Li, Wenying Guan, Xin Kang, Haixia Zhao. Advances on the mechanism of glaucoma filtration surgery scarring and anti-scarring treatment[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2021, 11(03): 188-192.

青光眼已成为全球范围内不可逆致盲的首要因素。眼压的病理性升高是青光眼最为危险的因素之一，由此可导致特征性视神经损伤。在过去的50年里，青光眼滤过术作为降低青光眼眼压的主要治疗手段，但其术后常因滤过泡瘢痕化，滤过通道房水流出受阻，导致手术失败。因此，明确青光眼滤过术后抗瘢痕化的机制对青光眼的治疗至关重要。本文中笔者就国内外针对瘢痕化形成的信号通路与当前抗瘢痕化治疗方法的研究进行综述，旨在为提高手术的成功率和临床新药开发提供新思路。

关键词: 青光眼, 成纤维细胞, 滤过泡, 抗瘢痕化

Glaucoma has become the leading cause of irreversible blindness in the world. The pathological increase in intraocular pressure is one of the most dangerous factor leading glaucoma, which would cause characteristic optic nerve damage. In the past 50 years, glaucoma filtering surgery has been the primary treatment for reducing glaucoma intraocular pressure. Glaucoma filtering surgery often scares the filtering bleb after the operation, which obstructing the outflow of aqueous humor through the filtering channel, causing the function to fail. To clarify, the anti-scarring mechanism after glaucoma filtering operation is essential for the treatment of glaucoma. Therefore, the research on scar formation signal pathways worldwide and the current anti-scarring treatment methods were reviewed in this paper, aiming to provide new ideas for improving surgery outcome and the development of new clinical drugs.

Key words: Glaucoma, Fibroblast, Filter bleb, Anti-scarring
图1 光学显微镜下苏木精-伊红染色兔行青光眼滤过术后的组织成像　可见滤过区成纤维细胞浸润，结缔组织较为紧密(箭头所指处，×100)
表1 药物输送系统的文献汇总
第一作者 输送系统 实验类别 作用机制 实验效果
Bulter等[53] 纳米银粒子 动物实验 减少组织间胶原沉积并抑制成纤维细胞增殖 较丝裂霉素-C阳性对照组更为显著
Qiao等[54] 光敏叠氮羟乙基壳聚糖水凝胶 动物实验 良好的水溶性及生物相容性 延长滤过通道的有效存在时间
Fili等[55] Ologen植入物 临床实验 良好的生物相容性 降低术后不良并发症的发生率
Ponnusamy等[56] 聚乳酸-乙醇酸多孔图层 细胞及动物实验 通过药物缓释作用持续抗瘢痕化 减少术后组织纤维化，提高手术成功率
[1]
Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis[J]. Ophthalmology, 2014, 121(11): 2081-2090.
[2]
崔巍，孙晓雷，李红霞. 蒙古族原发性闭角型青光眼小梁组织的超微结构[J]. 眼科研究，2010，28(7)：650-653.
[3]
孔亚男，陆宏，陈颖，等. 青光眼滤过术后瘢痕形成机制及抗瘢痕化研究进展[J]. 国际眼科杂志，2019，19(10)：1688-1691.
[4]
Stürmer JPE, Faschinger C. Do we perform glaucoma surgery too late？[J]. Klinische Monatsblatter fur Augenheilkunde, 2017, 235(11): 1269-1277.
[5]
于雪婷，孙兴怀. 青光眼手术滤过通道抗瘢痕化的药物研究[J]. 国际眼科纵览，2018，42(5)：289-296.
[6]
Li Z, van Bergen T, van de Veire S, et al. Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery[J]. Invest Ophthmol Vis Sci, 2009, 50(11): 5217-5225.
[7]
Zhang HT, Scott PAE, Morbidelli L, et al. The 121 amino acid isoform of vascular endothelial growth factor is more strongly tumorigenic than other splice variants in vivo[J]. British Journal of Cancer, 2000, 83(1): 63-68.
[8]
van Bergen T, Vandewalle E, van de Veire S, et al. The role of different VEGF isoforms in scar formation after glaucoma filtration surgery[J]. Exp Eye Res, 2011, 93(5): 689-699.
[9]
Canneliet P, Moons L, Luttun A, et al. Synergism between vascular endothelial growth factor and placental growth factor contfibutes to angiogenesis and plasma extravasation in pathological conditions[J]. Nat Med, 2001, 7(5): 575-583.
[10]
Lopilly PHY, Kim JH, Ahn MD, et al. Level of vascular endothelial growth factor in tenon tissue and results of glaucoma surgery[J]. Arch Ophthalmol, 2012, 130(6)：685-689.
[11]
张大卫. 兔眼青光眼滤过术后手术区组织TGF-B1、bFGF表达的实验研究[D]. 天津：天津医科大学，2004.
[12]
Stahnke T, Kowtharapu BS, Stachs O, et al. Suppression of TGF-β pathway by pirfenidone decreases extracellular matrix deposition in ocular fibroblastsin vitro[J]. PLoS One, 2017, 12(2): e0172592.
[13]
李静，谢安明. 结缔组织生长因子对人Tenon囊成纤维细胞中E-cadherin蛋白表达的促进作用[J]. 中华实验眼科杂志，2015，33(8)：695-698.
[14]
Weng HL, Wang BE, Jia JD, et al. Effect of interferon-gamma on hepatic fibrosis in chronic hepatitis B virus infection: a randomized controlled study[J]. Clinical Gastroenterology and Hepatology, 2005, 3(8): 819-828.
[15]
Wang XY, Crowston JG, Zoellner H, et al. Interferon-α and interferon-γ sensitize human tenon fibroblasts to mitomycin-C[J]. Invest Ophthmol Vis Sci, 2007, 48(8): 3655-3661.
[16]
Cui W, Zhang H, Liu ZL. Interleukin-6 receptor blockade suppresses subretinal fibrosis in a mouse model[J]. Int J Ophthal, 2014, 7(2): 194-197.
[17]
Farooqi AA, Waseem S, Riaz AM, et al. PDGF: the nuts and bolts of signalling toolbox[J]. Tumor Biology, 2011, 32(6): 1057-1070.
[18]
Dadrich M, Nicolay NH, Flechsig P, et al. Combined inhibition of TGFβ and PDGF signaling attenuates radiation-induced pulmonary fibrosis[J]. Oncoimmunology, 2016, 5(5): e1123366.
[19]
Siedlecki J, Asani B, Wertheimer C, et al. Combined VEGF/PDGF inhibition using axitinib induces αSMA expression and a pro-fibrotic phenotype in human pericytes[J]. Graefes Arch Clin Exp Ophthalmol, 2018, 256(6): 1141-1149.
[20]
Fuller JR. Anti-inflammatory fibrosis suppression in threatened trabeculectomy bleb failure produces good long term control of intraocular pressure without risk of sight threatening complications[J]. Brit J Ophthalmol, 2002, 86(12)：1352-1354.
[21]
Koval MS, Moster MR, Freidl KB, et al. Intracameral triamcinolone acetonide in glaucoma surgery: a prospective randomized controlled trial[J]. Am J Ophthal, 2014, 158(2)：395-401.
[22]
Na JH, Sung KR, Jin AS, et al. Antifibrotic effects of pirfenidone on Tenon′s fibroblasts in glaucomatous eyes: comparison with mitomycin C and 5-fluorouracil[J]. Graefes Arch Clin Exp Ophthalmol, 2015, 253 (9)：1537-1545.
[23]
Lama PJ, Fechtner RD. Antifibrotics and wound healing in glaucoma surgery[J]. Surv Ophthalmol, 2003, 48(3): 314-346.
[24]
郑露，李杜军，罗继红. 青光眼滤过手术抗瘢痕化药物和治疗方法的研究进展[J]. 中西医结合研究，2014，6(5)：266-269.
[25]
Green E, Wilkins M, Bunce C, et al. 5-Fluorouracil for glaucoma surgery[J]. Cochrane Database of Systematic Reviews, 2014: CD001132.
[26]
Lindemann F, Plange N, Kuerten D, et al. Three-year follow-up of trabeculectomy with 5-fluorouraeil[J]. Ophthalmic Res, 2017, 58 (2): 74-80.
[27]
Rao A, Chatterjee S. Epiconjunetival mitomyein C application for early failing filtering blebs[J]. Semin Ophthalmol, 2014, 29(1): 48-51.
[28]
Edward D, A1 Habash A, Aljasim L, et al. A review of the efficacy of mitomycin C in glaucoma filtration surgery[J]. Clin Ophthalmol, 2015, 9: 1945-1951.
[29]
Khouri SA, Huang G, Huang YL. Intraoperative injection vs sponge applied mitomyein C during trabeculectomy: one-year study[J]. J Curt Glaucoma Praet, 2017, 11(3): 101-106.
[30]
Lim MC, Hom B, Watnik MR, et al. A comparison of trabeculectomy surgery outcomes with mitomycin-C applied by intra-Tenon injection versus sponge[J]. Am J Ophthal, 2020, 216: 243-256.
[31]
Halili A, Kessel L, Subhi Y, et al. Needling after trabeculectomy——does augmentation by anti-metabolites provide better outcomes and is mitomycin C better than 5-fluoruracil? A systematic review with network meta-analyses[J]. Acta Ophthalmologica, 2020, 98(7): 643-653.
[32]
Akarsu C, Onol MB. Postoperative 5-fluorouracil versus intraoperative mitomycin C in high-risk glaucoma filtering surgery: extended follow up[J]. Clin Exp Ophthalmol, 2010, 31(3)：199-205.
[33]
Pimentel E, Schmidt J. Is mytomicyn better than 5-fluorouracil as antimetabolite in trabeculectomy for glaucoma? [J] Medwave, 2018, 18(1)：e7137.
[34]
张绍丹，吴作红. 5-氟尿嘧啶结膜下注射致全身性变态反应一例[J]. 中华实验眼科杂志，2019，37(10)：791-792.
[35]
方立建，魏文斌. 康柏西普玻璃体腔内注射联合阈值下微脉冲激光治疗糖尿病黄斑水肿的临床研究[J]．中华眼科医学杂志(电子版)，2020，10(2)：90-96.
[36]
马建民，赵家良. 转化生长因子β及其在青光眼术后滤过泡瘢痕化中作用的研究进展[J]. 国外医学(眼科学分册)，2004，28(5)：320-323.
[37]
Md-Noh SM, Sheikh AKSH, Bannur ZM, et al. Effects of ranibizumab on the extracellular matrix production by human Tenon′s fibroblast[J]. Exp Eye Res, 2014, 127：236-242.
[38]
Cheng JW, Cheng SW, Wei RL, et al. Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery[J]. Cochrane Database of Systematic Reviews (Online), 2016: CD009782.
[39]
Miraftabi A, Nilforushan N. Wound dehiscence and device migration after subconjunctival bevacizumab injection with Ahmed glaucoma valve implantation[J]. J Ophthalmic Vis Res, 2016, 11(1): 112-115.
[40]
Turgut B, Eren K, Akin MM, et al. Impact of trastuzumab on wound healing in experimental glaucoma surgery[J]. Clin Exp Ophthalmol, 2015, 43(1): 67-76.
[41]
Liu X, Yang Y, Guo X, et al. The antiangiogenesis effect of pirfenidone in wound healing in vitro[J]. J Ocul Pharmacol Ther, 2017, 33(9): 693-703.
[42]
胡佩宏. 吡非尼酮抑制兔眼抗青光眼滤过性手术后外引流通道瘢痕化的实验研究[D]. 南昌：南昌大学，2016.
[43]
Cordeiro MF, Gay JA, Khaw PT. Human anti-transforming growth factor-β2 antibody: a new glaucoma anti-scarring agent[J]. Invest Ophthmol Vis Sci, 1999, 40(10): 2225-2234.
[44]
CAT-152 0102 Trabeculectomy Study Group. A phase Ⅲ study of subconjunctival human anti-transforming growth factor β2 monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy[J]. Ophthalmology, 2007, 114(10): 1822-1830.
[45]
Fu S, Wang H, Zhang J, et al. Overexpression of ALK5 induces human Tenon′s capsule fibroblasts transdifferentiation and fibrosis in vitro[J]. Cur Eye Res, 2017, 42(7): 1018-1028.
[46]
Seet LF, Toh LZ, Finger SN, et al. Valproic acid suppresses collagen by selective regulation of Smads in conjunctival fibrosis[J]. J Mol Med, 2016, 94(3): 321-334.
[47]
Yan Z, Bai Y, Tian Z, et al. Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery[J]. Molecular Vision, 2011, 17: 2495.
[48]
Adachi K, Asada Y, Hirakata T, et al. Alteration of gene expression in mice after glaucoma filtration surgery[J]. Sci Rep, 2020, 10: 15036.
[49]
Heatley G, Kiland J, Faha B, et al. Gene therapy using p21WAF-1/Cip-1 to modulate wound healing after glaucoma trabeculectomy surgery in a primate model of ocular hypertension[J]. Gene Ther, 2004, 11(12): 949-955.
[50]
Li Z, Wen H, , Li X, et al. Suppression of human tenon fibroblast cell proliferation by lentivirus-mediated vegf small hairpin RNA[J]. J Ophthal, 2017, 17：7982051.
[51]
Li N, Cui J, Duan X, et a1. Suppression of type I collagen expression by mi R-29b via P13K, Akt, and Spl pathway in human Tenong fibroblasts[J]. Invest Ophthalmol Vis Sci, 2012, 53(3): 1670-1678.
[52]
Pfeiffer N, Voykov B, Renieri G, et al. First-in-human phase I study of ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in subjects with open-angle glaucoma undergoing glaucoma filtration surgery[J]. PloS One, 2017, 12(11): e0188899.
[53]
Butler MR, Ponce CMP, Weinstock YE, et al. Topical silver nanoparticles result in improved bleb function by increasing filtration and reducing fibrosis in a rabbit model of filtration surgery[J]. Invest Ophthmol Vis Sci, 2013, 54(7): 4982-4990.
[54]
Qiao X, Peng X, Qiao J, et al. Evaluation of a photo-crosslinkable hydroxyethyl chitosan hydrogel as a potential drug release system for glaucoma surgery[J]. J Mater Sci, 2017, 28(10): 149-159.
[55]
Fili S, Seddig S, Kohlhaas M. Long-term results after trabe-culectomy combined with mitomycin C and Ologen implant[J]. Klinische Monatsblatter fur Augenheilkunde, 2018, 236(9): 1107-1114.
[56]
Ponnusamy T, Yu H, John VT, et al. A novel antiproliferative drug coating for glaucoma drainage devices[J]. J Glaucoma, 2014, 23(8): 526-534.
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