Hereditary glaucoma: clinical and genetic characteristics

The review is devoted to the genetic nature of congenital glaucoma (CG) and presents clinical and genetic forms of hereditary glaucoma and single nucleotide polymorphisms identified by genome-wide association studies (GWAS). Glaucoma is a genetically heterogeneous disease, and patients with the same clinical diagnosis often have different molecular causes. The role of mutations in the CYP1B1 gene has been proven in the pathogenesis of hydrophthalmos; the MYOC gene — in juvenile open-angle glaucoma; the PAX6 gene — in aniridia; mutations in the PITX2, FOXC1 genes have been identified in Axenfeld-Rieger anomaly/syndrome. It has been established that 4–43% of patients with open-angle glaucoma have a family history of a mutation in the MYOC, OPTN or TBK1 genes. Genetic studies of glaucoma are the first steps to developing a new generation of personalized treatments. The article describes the key features of the pathogenesis of various genetic forms of glaucoma and the possible course of its therapy. However, gene therapy requires further study of both long-term effects and efficacy. Molecular genetic diagnosis of glaucoma allows for personalized genetic counseling of family members with consideration of the genetic risks.

1. Clinical guidelines "Congenital glaucoma". Moscow, 2017.

2. National Guidelines for Glaucoma. Edited by Egorov E.A., Erichev V.P. Moscow, GEOTAR-Media Publ., 2019. 384 p.

3. Ophthalmology: textbook. Edited by Egorov E.A. 3rd ed., revised and augmented. Moscow, GEOTAR-Media Publ., 2023. 312 р. https://doi.org/10.33029/9704-7114-2-oph-2023-1-312

4. Traboulsi E.I. Genetic diseases of the eye. Second edition. Oxford university press, 2012. 994 p.

5. Xiaoyi R.G. Genetics and genomics of eye disease, Advancing to Precision Medicine. Academic Press is an imprint of Elsevier, 2020. 383 p.

6. Liu Y., Allingham R.R. Major review: Molecular genetics of primary open-ang. glaucoma. Exp Eye Res 2017; 160:62-84. https://doi.org/10.1016/j.exer.2017.05.002

7. V.C. Sheffield, E.M. Stone, W.L. Alward et al. Genetic linkage of familial open-angle glaucoma to chromosome 1q21-q31. Natura Genetics 1993; 4(1):47-50. https://doi.org/10.1038/ng0593-47

8. E.M. Stone, J.H. Fingert, W.L. Alward et al. Identification of a gene that causes primary open-angle glaucoma. Science 1997; 275(5300): 668-670. https://doi.org/10.1126/science.275.5300.668

9. D. Stoilova, A. Child, O.C. Trifan et al. Localization of a locus (GLC1B) for adult-onset primary open-angle glaucoma to the 2cen-q13 region. Genomics 1996; 36(1):142-50. https://doi.org/10.1006/geno.1996.0434

10. Charlesworth J.C., Stankovich J.M., Mackey D.A. et al. Confirmation of the adult-onset primary open-angle glaucoma locus GLC1B at 2cen-q13 in an Australian family. Ophthalmologica 2006; 220(1):23-30. https://doi.org/10.1159/000089271

11. Akiyama M. , Yatsu K., Ota M. et al. Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma. British Journal of Ophthalmology 2008; 92(9):1293-1296. https://doi.org/10.1136/bjo.2008.139980

12. Wirtz M.K., Samples J.R., Kramer P.L. et al. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q. American Journal of Human Genetics 1997; 60(2):296-304.

13. Kitsos G., Eiberg H., Economou-Petersen E. et al. Genetic linkage of autosomal dominant primary open-angle glaucoma to chromosome 3q in a Greek pedigree. European Journal of Human Genetics 2001; 9(6):452-457. https://doi.org/10.1038/sj.ejhg.5200645

14. Gartaganis S.P., Georgakopoulos C.D., Assouti M. et al. Changes in HNK-1 epitope and collagen type IX in the aqueous humour of patients with pseudoexfoliation syndrome. Current Eye Research 2004; 28(1):5-10. https://doi.org/10.1076/ceyr.28.1.5.23490

15. Aga M., Bradley J.M., Wanchu R. et al. Differential effects of caveolin-1 and -2 knockdown on aqueous outflow and altered extracellular matrix turnover in caveolin-silenced trabecular meshwork cells. Investigative Ophthalmology and Visual Science 2014; 55(9):5497-509. https://doi.org/10.1167/iovs.14-14519.

16. Trifan O.C., Traboulsi E.I., Stoilova D. et al. A third locus (GLC1D) for adult-onset primary open-angle glaucoma maps to the 8q23 region. American Journal of Ophthalmology 1998; 126(1):17-28. https://doi.org/10.1016/s0002-9394(98)00073-7.

17. Sarfarazi M., Child A., Stoilova D. et al. Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region. American Journal of Human Genetics 1998; 62(3):641-652. https://doi.org/10.1086/301767.

18. Rezaie T., Child A., Hitchings R. et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 2002; 295(5557):1077-1079. https://doi.org/10.1126/science.1066901

19. Wirtz M.K., Samples J.R., Rust K. et al. GLC1F, a new primary open-angle glaucoma locus, maps to 7q35-q36. Archives of Ophthalmology 1999; 117(2):237-241. https://doi.org/10.1001/archopht.117.2.237.

20. Pasutto F., Keller K.E., Weisschuh N. et al. Variants in ASB10 are associated with open-angle glaucoma. Human Molecular Genetics 2012; 21(6):1336-1349. https://doi.org/10.1093/hmg/ddr572

21. Monemi S., Spaeth G., DaSilva A. et al. Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1. Human Molecular Genetics 2005; 14(6):725-733. https://doi.org/10.1093/hmg/ddi068

22. Suriyapperuma S.P., Child A., Desai T. et al. A new locus (GLC1H) for adult-onset primary open-angle glaucoma maps to the 2p15-p16 region. Archives of Ophthalmology 2007; 125(1):86-92. https://doi.org/10.1001/archopht.125.1.86.

23. Lin Y., Liu T., Li J. et al. A genome-wide scan maps a novel autosomal dominant juvenile-onset open-angle glaucoma locus to 2p15-16. Molecular Vision 2008; 14:739-744.

24. Mackay D.S., Bennett T.M., Shiels A. Exome sequencing identifies a missense variant in EFEMP1 co-segregating in a family with autosomal dominant primary open-angle glaucoma. PLoS One 2015; 10(7):e0132529. https://doi.org/10.1371/journal.pone.0132529

25. Wiggs J.L., Allingham R.R., Hossain A. et al. Genome-wide scan for adult onset primary open angle glaucoma. Human Molecular Genetics 2000; 9(7):1109-1117. https://doi.org/10.1093/hmg/9.7.1109

26. Allingham R.R., Wiggs J.L., Hauser E.R. et al. Early adult-onset POAG linked to 15q11-13 using ordered subset analysis. Investigative Ophthalmology and Visual Science 2005; 46(6):2002-2005. https://doi.org/10.1167/iovs.04-1477

27. Woodroffe A., Krafchak C.M., Fuse N. et al. Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in families with earlier adult age at diagnosis. Experimental Eye Research 2006; 82(6):1068-1074. https://doi.org/10.1016/j.exer.2005.10.008.

28. Crooks K.R., Allingham R.R., Qin X. et al. Genome-wide linkage scan for primary open angle glaucoma: influences of ancestry and age at diagnosis. PLoS One 2011; 6(7):e21967. https://doi.org/10.1371/journal.pone.0021967

29. Wiggs J.L., Lynch S., Ynagi G. et al. A genomewide scan identifies novel early-onset primary open-angle glaucoma loci on 9q22 and 20p12. American Journal of Human Genetics 2004; 74(6):1314-1320. https://doi.org/10.1086/421533

30. Baird P.N., Foote S.J., Mackey David A. et al. Evidence for a novel glaucoma locus at chromosome 3p21-22. Human Genetics 2005; 117(2-3):249-257. https://doi.org/10.1007/s00439-005-1296-x

31. Pang C.P., Fan B.J., Canlas O. et al. A genome-wide scan maps a novel juvenile-onset primary open angle glaucoma locus to chromosome 5q. Molecular Vision 2006; 12:85-92.

32. Fan B., Ko W.C., Wang D.Y. et al. Fine mapping of new glaucoma locus GLC1M and exclusion of neuregulin 2 as the causative gene. Molecular Vision 2007; 13:779-84.

33. Wang D.Y., Fan B.J., Chua J.K.H. et al. A genome-wide scan maps a novel juvenile-onset primary open-angle glaucoma locus to 15q. Investigative Ophthalmology and Visual Science 2006; 47(12):5315-5321. https://doi.org/10.1167/iovs.06-0179

34. Pasutto F., Matsumoto T., Mardin C.Y. et al. Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma. American Journal of Human Genetics 2009; 85(4):447-456. https://doi.org/10.1016/j.ajhg.2009.08.016

35. Liu Y., Liu W., Crooks K. et al. No evidence of association of heterozygous NTF4 mutations in patients with primary open-angle glaucoma. American Journal of Human Genetics 2010; 86(3):498-499. https://doi.org/10.1016/j.ajhg.2009.11.018

36. Vithana E.N., Nongpiur M.E., Venkataraman D. et al. Identification of a novel mutation in the NTF4 gene that causes primary open-angle glaucoma in a Chinese population. Molecular Vision 2010; 16:1640-1645.

37. Bennett S.R., Alward W.L., Folberg R. An autosomal dominant form of low-tension glaucoma. American Journal of Ophthalmology 1989; 108(3):238-244. https://doi.org/10.1016/0002-9394(89)90112-8

38. Fingert J.H., Robin A.L., Stone J.L. et al. Copy number variations on chromosome 12q14 in patients with normal tension glaucoma. Human Molecular Genetics 2011; 20(12):2482-2494. https://doi.org/10.1093/hmg/ddr123

39. Ritch R., Darbro B., Menon G. et al. TBK1 gene duplication and normal-tension glaucoma. JAMA Ophthalmology 2014; 132(5):544-548. https://doi.org/10.1001/jamaophthalmol.2014.104

40. Starikova D.I., Churnosov M.I. Genetic studies in primary open-angle glaucoma (a review). RMJ Clinical Ophthalmology 2017; 18(1): 49-52. https://doi.org/10.21689/2311-7729-2017-17-1-49-52

41. Polansky J.R., Fauss D.J., Chen P. et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica 1997; 211(3):126-139. https://doi.org/10.1159/000310780

42. Nguyen T.D., Chen P., Huang W.D. et al. Gene structure and properties of TIGR, an olfactomedin-related glycoprotein cloned from glucocorticoid-induced trabecular meshwork cells. The Journal of Biological Chemistry 1998; 273(11):6341-6350. https://doi.org/10.1074/jbc.273.11.6341

43. Lütjen-Drecoll E., May C.A., Polansky J.R. et al. Localization of the stress proteins alpha B-crystallin and trabecular meshwork inducible glucocorticoid response protein in normal and glaucomatous trabecular meshwork. Investigative Ophthalmology and Visual Science 1998; 39(3):517-525.

44. Jacobson N., Andrews M., Shepard A.R. et al. Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor. Human Molecular Genetics 2001; 10(2):117-125. https://doi.org/10.1093/hmg/10.2.117

45. O'Brien T.E., Metheney C.D., Polansky J.R. Immunofluorescence method for quantifying the trabecular meshwork glucocorticoid response (TIGR) protein in trabecular meshwork and Schlemm's canal cells. Current Eye Research 1999; 19(6):517-24. https://doi.org/10.1076/ceyr.19.6.517.5285

46. Kwon Y.H., Fingert J.H., Kuehn M.H., Alward W.L.M. Primary open-angle glaucoma. The New England Journal of Medicine 2009; 360(11):1113-1124. https://doi.org/10.1056/NEJMra0804630

47. Wiggs J.L., Haines J.L., Paglinauan C. et al. Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees. Genomics 1994; 21(2):299-303. https://doi.org/10.1006/geno.1994.1269

48. Richards J.E., Lichter P.R., Boehnke M. et al. Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome Iq. American Journal of Human Genetics 1994; 54(1):62-70.

49. Alward W.L., Fingert J.H., Coote M.A. et al. Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A). The New England Journal of Medicine 1998; 338(15):1022-1027. https://doi.org/10.1056/NEJM199804093381503

50. Fingert J.H., Héon E., Liebmann J.M. et al. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Human Molecular Genetics 1999; 8(5):899-905. https://doi.org/10.1093/hmg/8.5.899

51. Wiggs J.L., Allingham R.R., Vollrath D. et al. Prevalence of mutations in TIGR/Myocilin in patients with adult and juvenile primary open-angle glaucoma. American Journal of Human Genetics 1998; 63(5):1549-1552. https://doi.org/10.1086/302098

52. Stoilova D., Child A., Brice G. et al. Novel TIGR/MYOC mutations in families with juvenile onset primary open angle glaucoma. Journal of Medical Genetics 1998; 35(12):989-992. https://doi.org/10.1136/jmg.35.12.989

53. Adam M.F., Belmouden A., Binisti P. et al. Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Human Molecular Genetics 1997; 6(12):2091-2097. https://doi.org/10.1093/hmg/6.12.2091

54. Richards J.E., Ritch R., Lichter P.R. et al. Novel trabecular meshwork inducible glucocorticoid response mutation in an eight-generation juvenile-onset primary open-angle glaucoma pedigree. Ophthalmology 1998; 105(9):1698-1707. https://doi.org/10.1016/S0161-6420(98)99041-8

55. Brézin A.P., Adam M.F., Belmouden A. et al. Founder effect in GLC1A-linked familial open-angle glaucoma in Northern France. American Journal of Medical Genetics 1998; 76(5):438-445.

56. Craig J.E., Baird P.N., Healey D.L. et al. Evidence for genetic heterogeneity within eight glaucoma families, with the GLC1A Gln368STOP mutation being an important phenotypic modifier. Ophthalmology 2001; 108(9):1607-1620. https://doi.org/10.1016/s0161-6420(01)00654-6

57. Johnson A.T., Drack A.V., Kwitek A.E. et al. Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma. Ophthalmology 1993; 100(4):524-529. https://doi.org/10.1016/s0161-6420(13)31615-7

58. Johnson T., Richards J.E, Boehnke M. et al. Clinical phenotype of juvenile-onset primary open-angle glaucoma linked to chromosome 1q. Ophthalmology 1996;103(5):808-814. https://doi.org/10.1016/s0161-6420(96)30611-8

59. Mackey D.A., Healey D.L., Fingert J.H. et al. Glaucoma phenotype in pedigrees with the myocilin Thr377Met mutation. Archives of Ophthalmology 2003; 121(8):1172-1180. https://doi.org/10.1001/archopht.121.8.1172

60. Zode G.S., Kuehn M.H., Nishimura D.Y. et al. Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma. The Journal of Clinical Investigation 2011; 121(9):3542-3553. https://doi.org/10.1172/JCI58183

61. Zode G.S., Bugge K.E., Mohan K. et al. Topical ocular sodium 4-phenylbutyrate rescues glaucoma in a myocilin mouse model of primary open-angle glaucoma. Investigative Ophthalmology and Visual Science 2012; 53(3):1557-1565. https://doi.org/10.1167/iovs.11-8837

62. Burnight E.R., Giacalone J.C., Cooke J.A. et al. CRISPR-Cas9 genome engineering: Treating inherited retinal degeneration. Progress in Retinal and Eye Research 2018; 65:28-49. https://doi.org/10.1016/j.preteyeres.2018.03.003

63. Jain A., Zode G., Kasetti R.B. et al. CRISPR-Cas9-based treatment of myocilin-associated glaucoma. Proceedings of the National Academy of Science of the United States of America 2017; 114(42):11199-11204. https://doi.org/10.1073/pnas.1706193114

64. Aung T., Rezaie T., Okada K. et al. Clinical features and course of patients with glaucoma with the E50K mutation in the optineurin gene. Investigative Ophthalmology and Visual Science 2005; 46(8): 2816-22. https://doi.org/10.1167/iovs.04-1133

65. Hauser M.A., Sena D.F., Flor J. et al. Distribution of optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States. Journal of Glaucoma 2006; 15(5):358-363. https://doi.org/10.1097/01.ijg.0000212255.17950.42

66. Ying H., Yue Beatrice Y.J.T. Optineurin: The autophagy connection. Experimental Eye Research 2016; 144:73-80. https://doi.org/10.1016/j.exer.2015.06.029

67. Swarup G., Sayyad Z. Altered Functions and Interactions of Glaucoma-Associated Mutants of Optineurin. Frontires in Immunology 2018; 9:1287. https://doi.org/10.3389/fimmu.2018.01287

68. Li Y., Kang J., Horwitz M.S. Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains. Molecular and Cellular Biology 1998; 18(3):1601-1610. https://doi.org/10.1128/MCB.18.3.1601

69. Kroeber M., Ohlmann A., Russell P., Tamm E.R. Transgenic studies on the role of optineurin in the mouse eye. Experimental Eye Research 2006; 82(6):1075-1085. https://doi.org/10.1016/j.exer.2005.11.004

70. De Marco N., Buono M., Troise F., Diez-Roux G. Optineurin increases cell survival and translocates to the nucleus in a Rab8-dependent manner upon an apoptotic stimulus. The Journal of Biological Chemistry 2006; 281(23):16147-16156. https://doi.org/10.1074/jbc.M601467200

71. Alward W.L.M., Kwon Y.H., Kawase K. et al. Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma. American Journal of Ophthalmology 2003; 136(5):904-910. https://doi.org/10.1016/s0002-9394(03)00577-4

72. Fuse N., Takahashi K., Akiyama H. et al. Molecular genetic analysis of optineurin gene for primary open-angle and normal tension glaucoma in the Japanese population. Journal of Glaucoma 2004; 13(4):299-303. https://doi.org/10.1097/00061198-200408000-00007

73. Ayala-Lugo R.M., Pawar H., Reed D.M. et al. Variation in optineurin (OPTN) allele frequencies between and within populations. Molecular Vision 2007; 13:151-163.

74. Wiggs J. L., Auguste J., Allingham R.R. et al. Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma. Archives of Ophthalmology 2003; 121(8):1181-1183. https://doi.org/10.1001/archopht.121.8.1181

75. Willoughby C.E., Chan L.L.Y., Herd S. et al. Defining the pathogenicity of optineurin in juvenile open-angle glaucoma. Investigative Ophthalmology and Visual Science 2004; 45(9):3122-3130. https://doi.org/10.1167/iovs.04-0107

76. Kawase K., Allingham R.R., Meguro A. et al. Confirmation of TBK1 duplication in normal tension glaucoma. Experimental Eye Research 2012; 96(1):178-180. https://doi.org/10.1016/j.exer.2011.12.021

77. Awadalla M.S., Fingert J.H., Roos B.E. et al. Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma. American Journal of Ophthalmology 2015; 159(1):124-130.e1. https://doi.org/10.1016/j.ajo.2014.09.044

78. Kaurani L.,Vishal M., Ray J. et al. TBK1 duplication is found in normal tension and not in high tension glaucoma patients of Indian origin. Journal of Genetics 2016; 95(2):459-461. https://doi.org/10.1007/s12041-016-0637-y

79. Liu Y., Garrett M.E., Yaspan B.L. et al. DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma. Investigative Ophthalmology and Visual Science 2014; 55(12):8251-8258. https://doi.org/10.1167/iovs.14-15712

80. Fingert J.H., Robin A.L., Scheetz T. E. et al. Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis). Transactions of the American Ophthalmological Society 2016; 114:T6.

81. Louis C., Burns C., Wicks I. TANK-Binding Kinase 1-Dependent Responses in Health and Autoimmunity. Frontiers in Immunology 2018; 9:434. https://doi.org/10.3389/fimmu.2018.00434

82. Tojima Y., Fujimoto A., Delhase M. et al. NAK is an IkappaB kinase-activating kinase. Nature 2000; 404(6779):778-782. https://doi.org/10.1038/35008109

83. Bonnard M., Mirtsos C., Suzuki S. et al. Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription. The EMBO Journal 2000; 19(18):4976-4985. https://doi.org/10.1093/emboj/19.18.4976

84. Pomerantz J.L., Baltimore D. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. D. The EMBO Journal 1999; 18(23):6694-6704. https://doi.org/10.1093/emboj/18.23.6694

85. Moore A.S., Holzbaur E.L.F. Spatiotemporal dynamics of autophagy receptors in selective mitophagy. Autophagy 2016; 12(10):1956-1957. https://doi.org/10.1080/15548627.2016.1212788

86. 86 Fingert J.H., Darbro B.W., Qian Q. et al. TBK1 and flanking genes in human retina. Ophthalmic Genetics 2014; 35(1):35-40. https://doi.org/10.3109/13816810.2013.768674

87. 87 Tucker B.A., Solivan-Timpe F., Roos Ben R. et al. Duplication of TBK1 Stimulates Autophagy in iPSC-derived Retinal Cells from a Patient with Normal Tension Glaucoma. Journal of Stem Cell Research and Therapy 2014; 3(5):161. https://doi.org/10.4172/2157-7633.1000161

88. Wild P., Farhan H., McEwan D. G. et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 2011; 333(6039):228-233. https://doi.org/10.1126/science.1205405

89. Minegishi Y., Nakayama M., Iejima D. et al. Significance of optineurin mutations in glaucoma and other diseases. Progress in Retinal and Eye Research 2016; 55:149-181. https://doi.org/10.1016/j.preteyeres.2016.08.002

90. Toda Y., Tang S., Kashiwagi K. et al. Mutations in the optineurin gene in Japanese patients with primary open-angle glaucoma and normal tension glaucoma. American Journal of Medical Genetics Part A. 2004; 125A(1):1-4. https://doi.org/10.1002/ajmg.a.20439

91. Quigley H.A., Broman A.T. The number of people with glaucoma worldwide in 2010 and 2020. The British Journal of Ophthalmology 2006; 90(3):262-267. https://doi.org/10.1136/bjo.2005.081224

92. Funayama T., Ishikawa K., Ohtake Y. et al. Variants in optineurin gene and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma. Investigative Ophthalmology and Visual Science 2004; 45(12):4359-4367. https://doi.org/10.1167/iovs.03-1403

93. Reilly S.M., Chiang S.-H., Decker S.J. et al. An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice. Nature Medicine 2013; 19(3):313-321. https://doi.org/10.1038/nm.3082

94. Thorleifsson G., Walters G.B., Hewitt A.W. et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nature Genetics 2010; 42(10):906-909. https://doi.org/10.1038/ng.661

95. Bonnemaijer P.W.M., Iglesias A. I., Nadkarni G.N. et al. Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations. Human Genetics 2018; 137(10):847-862. https://doi.org/10.1007/s00439-018-1943-7

96. Hysi P.G., Cheng C.-Y., Springelkamp H. et al. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nature Genetics 2014; 46(10):1126-1130. https://doi.org/10.1038/ng.3087

97. Gu X., Reagan A.M., McClellan M. E., Elliott M.H. Caveolins and caveolae in ocular physiology and pathophysiology. Progress in Retinal and Eye Research 2017; 56:84-106. https://doi.org/10.1016/j.preteyeres.2016.09.005

98. Surgucheva I., Surguchov A. Expression of caveolin in trabecular meshwork cells and its possible implication in pathogenesis of primary open angle glaucoma. Molecular Vision 2011; 17:2878-2888.

99. Xiaoman L., McClellan M.E., Tanito M. et al. Loss of caveolin-1 impairs retinal function due to disturbance of subretinal microenvironment. Journal of Biological Chemistry 2012; 287(20):16424-16434. https://doi.org/10.1074/jbc.M112.353763

100. Scheetz T.E., Faga B., Ortega L. et al. Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study. Ophthalmology 2016; 123(12): 2527-2536. https://doi.org/10.1016/j.ophtha.2016.08.036

101. Sharma S., Burdon K.P., Chidlow G. et al. Association of genetic variants in the TMCO1 gene with clinical parameters related to glaucoma and characterization of the protein in the eye. Investigative Ophthalmology and Visual Science 2012; 53(8):4917-4925. https://doi.org/10.1167/iovs.11-9047

102. Chidlow G., Wood J. P.M., Sharma S. et al. Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region. PLoS One 2013; 8(9):e75067. https://doi.org/10.1371/journal.pone.0075067

103. Visel A., Zhu Y., May D. et al. Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice. Nature 2010; 464(7287):409-412. https://doi.org/10.1038/nature08801

104. Gao S., Jakobs T.C. Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure. American Journal of Pathology 2016; 186(4):985-1005. https://doi.org/10.1016/j.ajpath.2015.11.026

105. Bailey J.N.C., Loomis S.J., Kang J.H. et al. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nature Genetics 2016; 48(2):189-194. https://doi.org/10.1038/ng.3482

106. Ng S.K., Burdon K.P., Fitzgerald J.T. et al. Genetic Association at the 9p21 Glaucoma Locus Contributes to Sex Bias in Normal-Tension Glaucoma. Investigative Ophthalmology and Visual Science 2016; 57(7):3416-3421. https://doi.org/10.1167/iovs.16-19401

107. Ruf R.G., Xu P.-X., Silvius D. et al. SIX1 mutations cause branchio-otorenal syndrome by disruption of EYA1-SIX1-DNA complexes. Proceedings of the National Academy of Science of the United States of America 2004; 101(21):8090-8095. https://doi.org/10.1073/pnas.0308475101

108. Carnes M.U., Liu Y.P., Allingham R.R. et al. Discovery and functional annotation of SIX6 variants in primary open-angle glaucoma. PLoS Genetics 2014; 10(5):e1004372. https://doi.org/10.1371/journal.pgen.1004372

109. Williams S.E.I., Carmichael T. R., Allingham R.R. et al. The genetics of POAG in black South Africans: a candidate gene association study. Scientific Reports 2015; 5:8378. https://doi.org/10.1038/srep08378

110. Gharahkhani P., Burdon K.P, Fogarty R. et al. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nature Genetics 2014; 46(10):1120-1125. https://doi.org/10.1038/ng.3079

111. Caprioli J., Munemasa Y., Kwong J.M. K., Piri N. Overexpression of thioredoxins 1 and 2 increases retinal ganglion cell survival after pharmacologically induced oxidative stress, optic nerve transection. Transactions ot the American Ophthalmological Society 2009; 107:161-165.

112. Lattante S., Millecamps S., Stevanin G. et al. Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders. Neurology 2014; 83(11):990-995. https://doi.org/10.1212/WNL.0000000000000778