原发性开角型青光眼相关基因及发病机制研究进展

doi:10.3760/cma.j.issn.1674-845X.2019.10.013

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Abstract

Glaucoma is a type of optic neuropathy. It is the main cause of irreversible blindness in the world. Its pathogenesis is unclear at this time. In recent years, with the development of a genome-wide association study (GWAS), family studies and functional studies, great progress has been made in the understanding of the molecular basis and complexity of glaucoma. Primary open angle glaucoma (POAG) accounts for about 70% of glaucomatous cases worldwide and the prevalence rate has been increasing. POAG has obvious genetic characteristics, but since it is a complex genetic pattern, only about 10% of the cases represent a typical Mendelian single gene inheritance, and the others may be the interaction of multiple genetic factors, or the result of the common effects of genetic and environmental factors. At present, more than 30 genes directly related to glaucoma have been identified. The encoding proteins are involved in a wide range of cell processes and biological systems, including the extracellular matrix, cytokine signal transduction, lipid metabolism membrane biology, cell differentiation, autophagy and eye development. This report intends to further the understanding of the internal relationship between glaucoma and genes and clarify its possible pathogenesis from several important biological processes such as endoplasmic reticulum stress response, tumor necrosis factor-alpha signal pathway, autophagy regulation, TGF-beta signal pathway and others.

Key words： primary open angle glaucoma genes pathogenesis signal pathway

Received: 22 January 2019

Corresponding Authors: Xuyang Liu, Shenzhen Eye Hospital, School of Optometry, Shenzhen University, Shenzhen Key Laboratory of Ophthalmology, Shenzhen 518040, China; Xiamen Eye Center of Xiamen University, Xiamen 361005, China (Email: xliu1213@126.com)

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[1]	Jonas JB, Aung T, Bourne RR, et al. Glaucoma. Lancet, 2017, 390(10108): 2183-2193. DOI: 10.1016/S0140-6736(17)31469-1.
[2]	Beidoe G, Mousa SA. Current primary open-angle glaucoma treatments and future directions. Clin Ophthalmol, 2012, 6(1): 1699-1707. DOI: 10.2147/OPTH.S32933.
[3]	Kapetanakis VV, Chan M PY, Foster PJ, et al. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-
	analysis. Br J Ophthalmol, 2016, 100(1): 86-93. DOI: 10.1136/ bjophthalmol-2015-307223.
[4]	Danford ID, Verkuil LD, Choi DJ, et al. Characterizing the "POAGome": A bioinformatics-driven approach to primary open-angle glaucoma. Prog Retin Eye Res, 2017, 58: 89-114.
	DOI: 10.1016/j.preteyeres.2017.02.001.
[5]	Wiggs JL. Glaucoma Genes and Mechanisms. Prog Mol Biol Transl Sci, 2015, 134: 315-342. DOI: 10.1016/bs.pmbts.2015.04. 008.
[6]	Wiggs JL, Pasquale LR. Genetics of Glaucoma. Hum Mol Genet, 2017, 26(R1), R21-R27. DOI: 10.1093/hmg/ddx184.
[7]	Kwartler CS, Chen J, Thakur D, et al. Overexpression of smooth muscle myosin heavy chain leads to activation of the unfolded protein response and autophagic turnover of thick filament-associated proteins in vascular smooth muscle cells. J Biol Chem, 2014, 289(20): 14075-14088. DOI: 10.1074/jbc.M113. 499277.
[8]	Zhang SX, Ma JH, Bhatta M, et al. The unfolded protein response in retinal vascular diseases: implications and therapeutic potential beyond protein folding. Prog Retin Eye
	Res, 2015, 45: 111-131. DOI: 10.1016/j.preteyeres.2014.12.001.
[9]	Zode GS, Kuehn MH, Nishimura DY, et al. Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma. J Clin Invest, 2011, 121(9): 3542-3553. DOI: 10.1172/JCI58183.
[10]	Donegan RK, Hill SE, Freeman DM, et al. Structural basis for misfolding in myocilinassociated glaucoma. Hum Mol Genet, 2014, 24(8): 2111-2124. DOI: 10.1093/hmg/ddu730.
[11]	Alward WL, Fingert JH, Coote MA, et al. Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A). N Engl J Med, 1998, 338(15): 1022- 1027.DOI: 10.1056/NEJM199804093381503.
[12]	Chen X, Yan N, Yun H, et al. Sequence analysis of MYOC and CYP1B1 in a Chinese pedigree of juvenile glaucoma with goniodysgenesis. Mol Vis, 2009, 15(163): 1530-1536.
[13]	Kim BS, Savinova OV, Reedy MV, et al. Targeted disruption of the myocilin gene (Myoc) suggests that human glaucoma-causing mutations are gain of function. Mol Cell Biol, 2001,
21	(22): 7707-7713. DOI: 10.1128/MCB.21.22.7707-7713.2001.
[14]	Gould DB, Miceli-Libby L, Savinova OV, et al. Genetically increasing Myoc expression supports a necessary pathologic role of abnormal proteins in glaucoma. Mol Cell Biol, 2004, 24(20): 9019-9025. DOI: 10.1128/MCB.24.20.9019-9025.2004.
[15]	Zhou Z, Vollrath D. A cellular assay distinguishes normal and mutant TIGR/myocilin protein. Hum Mol Genet. 1999, 8: 2221- 2218. DOI: 10.1093/hmg/8.12.2221.
[16]	Filla MS, Liu X, Nguyen TD, et al. In vitro localization of TIGR/MYOC in trabecular meshwork extracellular matrix and binding to fibronectin. Invest Ophthalmol Vis Sci, 2002, 43(1):
15	1-161.
[17]	Joe MK, Sohn S, Hur W, et al. Accumulation of mutant myocilins in ER leads to ER stress and potential cytotoxicity in human trabecular meshwork cells. Biochem Biophys Res
	Commun, 2003, 312(3): 592-600. DOI: 10.1016/j.bbrc.2003.10. 162.
[18]	Kasetti RB, Phan TN, Millar JC, et al. Expression of mutant myocilin induces abnormal intracellular accumulation of selected extracellular matrix proteins in the trabecular meshwork. Invest Ophthalmol Vis Sci. 2016, 57(14): 6058-6069.DOI: 10.1167/ iovs.16-19610.
[19]	Prat C, Belville C, Comptour A, et al. Myocilin, expression is regulated by retinoic acid in the trabecular meshwork-derived cellular environment. Exp Eye Res, 2017, 155: 91-98. DOI: 10. 1016/j.exer.2017.01.006.
[20]	Kang JH, Wiggs JL, Pasquale LR. A nested case control study of plasma ICAM-1,E-selectin and TNF receptor 2 levels, and incident primary open-angle glaucoma. Invest Ophthalmol Vis Sci, 2013, 54(3): 1797-1804. DOI: 10.1167/iovs.12-11191.
[21]	Roh M, Zhang Y, Murakami Y, et al. Etanercept, a widely used inhibitor of tumor necrosis factor-α (TNF-α), prevents retinal ganglion cell loss in a rat model of glaucoma. PLoS One, 2012, 7(7): e40065. DOI: 10.1371/journal.pone.0040065.
[22]	Sudhakar C, Nagabhushana A, Jain N, Swarup G. NF-kappaB mediates tumor necrosis factor alpha-induced expression of optineurin, a negative regulator of NF-kappaB. PLoS One, 2009, 4(4): e5114. DOI: 10.1371/journal.pone.0005114.
[23]	Nagabhushana A, Bansal M, Swarup G. Optineurin is required for CYLD-dependent inhibition of TNFα-induced NF-κB activation. PLoS One, 2011, 6(3): e17477. DOI: 10.1371/journal. pone.0017477.
[24]	Kachaner D, Génin P, Laplantine E, Weil R. Toward an integrative view of Optineurin functions. Cell Cycle, 2012, 11(15): 2808-2818. DOI: 10.4161/cc.20946.
[25]	De MN, Buono M, Troise F, et al. Optineurin increases cell survival and translocates to the nucleus in a Rab8-dependent manner upon an apoptotic stimulus. J Biol Chem, 2006, 281(23): 16147-16156. DOI: 10.1074/jbc.M601467200.
[26]	Rezaie T, Child A, Hitchings R, et al. Adult-Onset Primary OpenAngle Glaucoma Caused by Mutations in Optineurin. Science, 2002, 295(5557): 1077-1079. DOI:10.1126/science.1066901.
[27]	Sarfarazi M, Rezaie T. Optineurin in primary open angle glaucoma. Ophthalmol Clin North Am, 2003, 16(4): 529-541. DOI: 10.1016/S0896-1549(03)00061-0.
[28]	Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol, 2010, 22(2): 124-131. DOI: 10.1016/j.ceb.2009.11.014.
[29]	Shen X, Ying H, Qiu Y, et al. Processing of optineurin in neuronal cells. J Biol Chem, 2011, 286(5): 3618-3629.DOI: 10. 1074/jbc.M110.175810.
[30]	Wong YC, Holzbaur EL. Temporal dynamics of PARK2/parkin and OPTN/optineurin recruitment during the mitophagy of damaged mitochondria. Autophagy, 2015, 11(2): 422-424. DOI: 10.1080/15548627.2015.1009792.
[31]	Ashrafi G, Schlehe JS, LaVoie MJ, Schwarz TL. Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J Cell Biol, 2014, 206(5): 655- 670. DOI: 10.1083/jcb.201401070.
[32]	Fuchshofer R. The pathogenic role of transforming growth factor-β2 in glaucomatous damage to the optic nerve head. Exp Eye Res, 2011, 93(2): 165-169. DOI: 10.1016/j.exer.2010.07. 014.
[33]	Pena JD, Taylor AW, Ricard CS, et al. Transforming growth factor beta isoforms in human optic nerve heads. Br J Ophthalmol, 1999, 83(2): 209-218.
[34]	Massagué J, Blain SW, Lo RS. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell, 2000, 103(2): 295- 309. DOI: 10.1016/S0092-8674(00)00121-5.
[35]	Ramdas WD, van Koolwijk LM, Lemij HG, et al. Common genetic variants associated with open-angle glaucoma. Hum Mol Genet, 2011, 20(12): 2464-2471. DOI: 10.1093/hmg/ddr120.
[36]	Dan C, Jiao X, Xing L, et al. CDKN2B Polymorphism is associated with primary open-angle glaucoma (POAG) in the Afro-Caribbean population of barbados, West Indies. PLoS One, 2012, 7(6): e39278. DOI: 10.1371/journal.pone.0039278.
[37]	Liu Y, Hauser MA, Akafo SK, et al. Investigation of known genetic risk factors for primary open angle glaucoma in two Populations of African ancestry. Invest Ophthalmol Vis Sci,
20	13, 54(9): 6248-6254. DOI: 10.1167/iovs.13-12779.
[38]	Li Z, Allingham RR, Nakano M, et al. A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet, 2015, 24(13): 3880-3892.DOI:10.1093/hmg/ddv128.
[39]	Pasmant E, Sabbagh A, Vidaud M, et al. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J, 2011, 25(2): 444. DOI: 10.1096/fj.10-172452.
[40]	Burdon KP, Macgregor S, Hewitt AW, et al. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nat Genet, 2011,
43	(6): 574-578. DOI: 10.1038/ng.824.
[41]	Blobe GC, Liu X, Fang SJ, et al. A novel mechanism for regulating transforming growth factor beta (TGF-beta) signaling. Functional modulation of type III TGF-beta receptor expression through interaction with the PDZ domain protein, GIPC. J Biol Chem, 2001, 276(43): 39608-39617. DOI: 10.1074/jbc. M106831200.
[42]	Cai C, Rajaram M, Zhou X, et al. Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogene FNDC3B. Cell Cycle, 2012, 11(9): 1773-1781. DOI: 10.4161/cc.20121.
[43]	Wax MB, Tezel G.Immunoregulation of retinal ganglion cell fate in glaucoma. Exp Eye Res, 2009, 88(4): 825-830. DOI: 10.1016/ j.exer.2009.02.005.
[44]	Hauser MA, Allingham RR, Linkroum K, et al. Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci, 2006, 47(6): 2542- 2546. DOI: 10.1167/iovs.05-1476.
[45]	Chi ZL, Yasumoto F, Sergeev Y, et al. Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice. Hum Mol Genet, 2010, 19(19): 3806-3815. DOI: 10.1093/hmg/ddq299.