Glaucoma: Genes, phenotypes, and new directions for therapy

Journal of Clinical Investigation

Volumn 120, Issue 9, 2010, Pages 3064-3072

  Fan, Bao Jian ^a   Wiggs, Janey L ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; GROWTH FACTOR; LEUCINE RICH REPEAT AND IG DOMAIN CONTAINING 1; UNCLASSIFIED DRUG;

AUTOSOMAL RECESSIVE INHERITANCE; CELL THERAPY; CLOSED ANGLE GLAUCOMA; CONGENITAL GLAUCOMA; CONSANGUINITY; DISEASE MARKER; GENE LOCUS; GENE THERAPY; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC SCREENING; GENETIC SUSCEPTIBILITY; GENOMICS; GLAUCOMA; HUMAN; INTRAOCULAR PRESSURE; MICROPHTHALMIA; NEUROPROTECTION; NONHUMAN; OPEN ANGLE GLAUCOMA; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; RETINA PIGMENT DEGENERATION; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; STEM CELL TRANSPLANTATION;

BLINDNESS; DISEASE PROGRESSION; EYE; FORECASTING; GENETIC LINKAGE; GLAUCOMA; HUMANS; INTRAOCULAR PRESSURE; OPTIC NERVE; PHENOTYPE; TONOMETRY, OCULAR;

EID: 77956370875     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI43085     Document Type: Review

References (144)

1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-267.
2. Appropriateness of Treating Glaucoma Suspects RAND Study Group. For which glaucoma suspects is it appropriate to initiate treatment? Ophthalmology. 2009;116(4):710-716.
3. Tamm ER. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res. 2009;88(4):648-655.
4. Mosaed S, Dustin L, Minckler DS. Comparative outcomes between newer and older surgeries for glaucoma. Trans Am Ophthalmol Soc. 2009;107:127-133.
5. Qu J, Wang D, Grosskreutz CL. Mechanisms of retinal ganglion cell injury and defense in glaucoma. Exp Eye Res. 2010;91(1):48-53.
6. Cheng JW, Cai JP, Wei RL. Meta-analysis of medical intervention for normal tension glaucoma. Ophthalmology. 2009;116(7):1243-1249.
7. Wiggs JL, Damji KF, Haines JL, Pericak-Vance MA, Allingham RR. The distinction between juvenile and adult-onset primary open-angle glaucoma. Am J Hum Genet. 1996;58(1):243-244.
8. Fan BJ, Wang DY, Lam DS, Pang CP. Gene mapping for primary open angle glaucoma. Clin Biochem. 2006;39(3):249-258.
9. Wiggs JL. Genetic etiologies of glaucoma. Arch Ophthalmol. 2007;125(1):30-37.
10. Sarfarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye (Lond). 2000;14(pt 3B):422-428.
11. Sarfarazi M, et al. Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity. Genomics. 1995;30(2):171-177.
12. Akarsu AN, et al. A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region. Hum Mol Genet. 1996;5(8):1199-1203.
13. Stoilov IR, Sarfarazi M. The third genetic locus (GLC3C) for primary congenital glaucoma (PCG) maps to chromosome 14q24.3. Invest Ophthalmol Vis Sci. 2002;43:e3015.
14. Firasat S, Riazuddin SA, Hejtmancik JF, Riazuddin S. Primary congenital glaucoma localizes to chromosome 14q24.2-24.3 in two consanguineous Pakistani families. Mol Vis. 2008;14:1659-1665.
15. Stoilov I, Akarsu AN, Sarfarazi M. Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet. 1997;6(4):641-647.
16. Ali M, et al. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009;84(5):664-671.
17. Narooie-Nejad M, et al. Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma. Hum Mol Genet. 2009;18(20):3969-3977.
18. Bejjani BA, et al. Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia. Am J Hum Genet. 1998;62(2):325-333.
19. Vasiliou V, Gonzalez FJ. Role of CYP1B1 in glaucoma. Annu Rev Pharmacol Toxicol. 2008;48:333-358.
20. Gould DB, Smith RS, John SW. Anterior segment development relevant to glaucoma. Int J Dev Biol. 2004;48(8-9):1015-1029.
21. Grosso S, et al. Familial Axenfeld-Rieger anomaly, cardiac malformations, and sensorineural hearing loss: a provisionally unique genetic syndrome? Am J Med Genet. 2002;111(2):182-186.
22. Semina EV, et al. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet. 1996;14(4):392-399.
23. Mears AJ, et al. Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. Am J Hum Genet. 1998;63(5):1316-1328.
24. van Heyningen V, Williamson KA. PAX6 in sensory development. Hum Mol Genet. 2002;11(10):1161-1167.
25. Dreyer SD, et al. Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat Genet. 1998;19(1):47-50.
26. Mimiwati Z, et al. Nail-patella syndrome and its association with glaucoma: a review of eight families. Br J Ophthalmol. 2006;90(12):1505-1509.
27. Saleem RA, Walter MA. The complexities of ocular genetics. Clin Genet. 2002;61(2):79-88.
28. Hjalt TA, Semina EV. Current molecular understanding of Axenfeld-Rieger syndrome. Expert Rev Mol Med. 2005;7(25):1-17.
29. Yalvac IS, Satana B, Ozkan G, Eksioglu U, Duman S. Management of glaucoma in patients with nanophthalmos. Eye (Lond). 2008;22(6):838-843.
30. Othman MI, et al. Autosomal dominant nanophthalmos (NNO1) with high hyperopia and angleclosure glaucoma maps to chromosome 11. Am J Hum Genet. 1998;63(5):1411-1418.
31. Sundin OH, et al. Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein. Proc Natl Acad Sci U S A. 2005;102(27):9553-9558.
32. Li H, et al. Localization of a novel gene for congenital nonsyndromic simple microphthalmia to chromosome 2q11-14. Hum Genet. 2008;122(6):589-593.
33. Won J, et al. Membrane frizzled-related protein is necessary for the normal development and maintenance of photoreceptor outer segments. Vis Neurosci. 2008;25(4):563-574.
34. Niyadurupola N, Broadway DC. Pigment dispersion syndrome and pigmentary glaucoma - a major review. Clin Experiment Ophthalmol. 2008;36(9):868-882.
35. Andersen JS, et al. A gene responsible for the pigment dispersion syndrome maps to chromosome 7q35-q36. Arch Ophthalmol. 1997;115(3):384-388.
36. Anderson MG, et al. Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nat Genet. 2002;30(1):81-85.
37. Lynch S, Yanagi G, DelBono E, Wiggs JL. DNA sequence variants in the tyrosinase-related protein 1 (TYRP1) gene are not associated with human pigmentary glaucoma. Mol Vis. 2002;8:127-129.
38. Wiggs JL, Damji KF, Haines JL, Pericak-Vance MA, Allingham RR. The distinction between juvenile and adult-onset primary open-angle glaucoma. Am J Hum Genet. 1996;58(1):243-244.
39. Johnson AT, et al. Clinical phenotype of juvenile-onset primary open-angle glaucoma linked to chromosome 1q. Ophthalmology. 1996;103(5):808-814.
40. Wiggs JL, Del Bono EA, Schuman JS, Hutchinson BT, Walton DS. Clinical features of five pedigrees genetically linked to the juvenile glaucoma locus on chromosome 1q21-q31. Ophthalmology. 1995;102(12):1782-1789.
41. Sheffield VC, et al. Genetic linkage of familial open angle glaucoma to chromosome 1q21-q31. Nat Genet. 1993;4(1):47-50.
42. Wiggs JL, et al. A genomewide scan identifies novel early-onset primary open-angle glaucoma loci on 9q22 and 20p12. Am J Hum Genet. 2004;74(6):1314- 1320.
43. Wang DY, et al. Absence of myocilin and optineurin mutations in a large Philippine family with juvenile onset primary open angle glaucoma. Mol Vis. 2004;10:851-856.
44. Pang CP, et al. A genome-wide scan maps a novel juvenile-onset primary open angle glaucoma locus to chromosome 5q. Mol Vis. 2006;12:85-92.
45. Fan BJ, et al. Fine mapping of new glaucoma locus GLC1M and exclusion of neuregulin 2 as the causative gene. Mol Vis. 2007;13:779-784.
46. Wang DY, et al. A genome-wide scan maps a novel juvenile-onset primary open-angle glaucoma locus to 15q. Invest Ophthalmol Vis Sci. 2006;47(12):5315-5321.
47. Stone EM, et al. Identification of a gene that causes primary open angle glaucoma. Science. 1997;275(5300):668-670.
48. Kubota R, et al. A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping. Genomics. 1997;41(3):360-369.
49. Wiggs JL, et al. Prevalence of mutations in TIGR/Myocilin in patients with adult and juvenile primary open-angle glaucoma. Am J Hum Genet. 1998;63(5):1549-1552.
50. Fingert JH, et al. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum Mol Genet. 1999;8(5):899-905.
51. Wiggs JL, Vollrath D. Molecular and clinical evaluation of a patient hemizygous for TIGR/MYOC. Arch Ophthalmol. 2001;119(11):1674-1678.
52. Kim BS, 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.
53. Resch ZT, Fautsch MP. Glaucoma-associated myocilin: a better understanding but much more to learn. Exp Eye Res. 2009;88(4):704-712.
54. Aroca-Aguilar JD, Martínez-Redondo F, Sánchez- Sánchez F, Coca-Prados M, Escribano J. Functional role of proteolytic processing of recombinant myocilin in self-aggregation. Invest Ophthalmol Vis Sci. 2010;51(1):72-78.
55. Joe MK, Tomarev SI. Expression of myocilin mutants sensitizes cells to oxidative stress-induced apoptosis. Implication for glaucoma pathogenesis. Am J Pathol. 2010;176(6):2880-2890.
56. Rezaie T, et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science. 2002;295(5557):1077-1079.
57. Hauser MA, et al. Distribution of optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States. J Glaucoma. 2006;15(5):358-363.
58. Aung T, et al. Clinical features and course of patients with glaucoma with the E50K mutation in the optineurin gene. Invest Ophthalmol Vis Sci. 2005;46(8):2816-2822.
59. Chalasani ML, Radha V, Gupta V, Agarwal N, Balasubramanian D, Swarup G. A glaucoma-associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants. Invest Ophthalmol Vis Sci. 2007;48(4):1607-1614.
60. Chibalina MV, Roberts RC, Arden SD, Kendrick-Jones J, Buss F. Rab8-optineurin-myosin VI: analysis of interactions and functions in the secretory pathway. Methods Enzymol. 2008;438:11-24.
61. Monemi S, et al. Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1. Hum Mol Genet. 2005;14(6):725-733.
62. Hauser MA, et al. Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2006;47(6):2542-2546.
63. Skarie JM, Link BA. The primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway. Hum Mol Genet. 2008;17(16):2474-2485.
64. Wiggs JL, et al. Genome-wide scan for adult onset primary open angle glaucoma. Hum Mol Genet. 2000;9(7):1109-1117.
65. Nemesure B, et al. A genome-wide scan for primary open-angle glaucoma (POAG): the Barbados Family Study of Open-Angle Glaucoma. Hum Genet. 2003;112(5-6):600-609.
66. Rotimi CN, et al. Genomewide scan and fine mapping of quantitative trait loci for intraocular pressure on 5q and 14q in West Africans. Invest Ophthalmol Vis Sci. 2006;47(8):3262-3267.
67. Allingham RR, et al. Early adult-onset POAG linked to 15q11-13 using ordered subset analysis. Invest Ophthalmol Vis Sci. 2005;46(6):2002-2005.
68. Pasutto F, et al. Heterozygous NTF4 mutations impairing neurotrophin-4 signaling in patients with primary open-angle glaucoma. Am J Hum Genet. 2009;85(4):447-456.
69. Kang JH, et al. Endothelial nitric oxide synthase gene variants and primary open-angle glaucoma: interactions with sex and postmenopausal hormone use. Invest Ophthalmol Vis Sci. 2010;51(2):971-979.
70. Konstas AG, Mantziris DA, Stewart WC. Diurnal intraocular pressure in untreated exfoliation and primary open-angle glaucoma. Arch Ophthalmol. 1997;115(2):182-185.
71. Thorleifsson G, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317(5843):1397-1400.
72. Fan BJ, et al. DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity. BMC Med Genet. 2008;9:5.
73. Pasutto F, et al. Association of LOXL1 common sequence variants in German and Italian patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci. 2008;49(4):1459-1463.
74. Hewitt AW, et al. Ancestral LOXL1 variants are associated with pseudoexfoliation in Caucasian Australians but with markedly lower penetrance than in Nordic people. Hum Mol Genet. 2008;17(5):710-716.
75. Lee KY, et al. Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese. Mol Vis. 2009;15:1120-1126.
76. Ozaki M, et al. Association of LOXL1 gene polymorphisms with pseudoexfoliation in the Japanese. Invest Ophthalmol Vis Sci. 2008;49(9):3976-3980.
77. Wiggs JL. Association Between LOXL1 and pseudoexfoliation. Arch Ophthalmol. 2008;126(3):420-421.
78. Liu X, et al. Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat Genet. 2004;36(2):178-182
79. Acott TS, Kelley MJ. Extracellular matrix in the trabecular meshwork. Exp Eye Res. 2008;86(4):543-561.
80. Urban Z, Agapova O, Hucthagowder V, Yang P, Starcher BC, Hernandez MR. Population differences in elastin maturation in optic nerve head tissue and astrocytes. Invest Ophthalmol Vis Sci. 2007;48(7):3209-3215.
81. Thomassin L, et al. The Pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. J Biol Chem. 2005;280(52):42848-42855.
82. Williams SE, et al. Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population. Mol Vis. 2010;16:705-712.
83. Nakano M, et al. Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population. Proc Natl Acad Sci U S A. 2009;106(31):12838-12842.
84. Jiao X, et al. Common variants on chromosome 2 and risk of primary open-angle glaucoma in the Afro-Caribbean population of Barbados. Proc Natl Acad Sci U S A. 2009;106(40):17105-17110.
85. Lindsey JD, Weinreb RN. Elevated intraocular pressure and transgenic applications in the mouse. J Glaucoma. 2005;14(4):318-320.
86. Libby RT, et al. Modification of ocular defects in mouse developmental glaucoma models by tyrosinase. Science. 2003;299(5612):1578-1581.
87. Bidinost C, et al. Of mice and men: tyrosinase modification of congenital glaucoma in mice but not in humans. Invest Ophthalmol Vis Sci. 2006;47(4):1486-1490.
88. Smith RS, et al. Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development. Hum Mol Genet. 2000;9(7):1021-1032.
89. Zhou Y, Grinchuk O, Tomarev SI. Transgenic mice expressing the Tyr437His mutant of human myocilin protein develop glaucoma. Invest Ophthalmol Vis Sci. 2008;49(5):1932-1939.
90. Chi ZL, et al. Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a progressive retinal degeneration in mice. Hum Mol Genet. 2010;19(13):2606-2615.
91. van Koolwijk LM, et al. Genetic contributions to glaucoma: heritability of intraocular pressure, retinal nerve fiber layer thickness, and optic disc morphology. Invest Ophthalmol Vis Sci. 2007;48(8):3669-3676.
92. van Koolwijk LM, et al. Major genetic effects in glaucoma: commingling analysis of optic disc parameters in an older Australian population. Invest Ophthalmol Vis Sci. 2009;50(11):5275-5280.
93. Klein BE, Klein R, Lee KE. Heritability of risk factors for primary open-angle glaucoma: the Beaver Dam Eye Study. Invest Ophthalmol Vis Sci. 2004;45(1):59-62.
94. Landers JA, et al. Heritability of central corneal thickness in nuclear families. Invest Ophthalmol Vis Sci. 2009;50(9):4087-4090.
95. Duggal P, Klein AP, Lee KE, Klein R, Klein BE, Bailey-Wilson JE. Identification of novel genetic loci for intraocular pressure: a genomewide scan of the Beaver Dam Eye Study. Arch Ophthalmol. 2007;125(1):74-79.
96. Dimasi DP, et al. Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes. Hum Genet. 2010;127(1):33-44.
97. Macgregor S, et al. Genome-wide association identifies ATOH7 as a major gene determining human optic disc size. Hum Mol Genet. 2010;19(13):2716-2724.
98. Mackey DA, Craig JE. Predictive DNA testing for glaucoma: reality in 2003. Ophthalmol Clin North Am. 2003;16(4):639-645.
99. Fan BJ, Tam PO, Choy KW, Wang DY, Lam DS, Pang CP. Molecular diagnostics of genetic eye diseases. Clin Biochem. 2006;39(3):231-239.
100. Golubnitschaja O, Flammer J. What are the biomarkers for glaucoma? Surv Ophthalmol. 2007;52(suppl 2):S155-S161.
101. Dervan EW, et al. Protein macroarray profiling of serum autoantibodies in pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci. 2010;51(6):2968-2975.
102. Honda N, et al. Effect of latanoprost on the expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 on the ocular surface. Arch Ophthalmol. 2010;128(4):466-471.
103. Johnson EC, Guo Y, Cepurna WO, Morrison JC. Neurotrophin roles in retinal ganglion ell survival: lessons from rat glaucoma models. Exp Eye Res. 2009;88(4):808-815.
104. Weber AJ, Viswanáthan S, Ramanathan C, Harman CD. Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury. Invest Ophthalmol Vis Sci. 2010;51(1):327-334.
105. Martin KR, et al. Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model. Invest Ophthalmol Vis Sci. 2003;44(10):4357-4365.
106. Fu QL, et al. Combined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma. Neuroscience. 2009;162(2):375-382.
107. Pease ME, et al. Effect of CNTF on retinal ganglion cell survival in experimental glaucoma. Invest Ophthalmol Vis Sci. 2009;50(5):2194-2200.
108. Lambiase A, et al. Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma. Proc Natl Acad Sci U S A. 2009;106(32):13469-13474.
109. Maguire AM, et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009;374(9701):1597-1605.
110. Liu X, Rasmussen CA, Gabelt BT, Brandt CR, Kaufman PL. Gene therapy targeting glaucoma: where are we? Surv Ophthalmol. 2009;54(4):472-486.
111. Spiga MG, Borras T. Development of a gene therapy virus with a glucocorticoid-inducible MMP1 for the treatment of steroid glaucoma. Invest Ophthalmol Vis Sci. 2010;51(6):3029-3041.
112. Barraza RA, McLaren JW, Poeschla EM. Prostaglandin pathway gene therapy for sustained reduction of intraocular pressure. Mol Ther. 2010;18(3):491-501.
113. Buie LK, et al. Self-complementary AAV virus (scAAV) safe and long-term gene transfer in the trabecular meshwork of living rats and monkeys. Invest Ophthalmol Vis Sci. 2010;51(1):236-248.
114. Bull ND, Johnson TV, Martin KR. Stem cells for neuroprotection in glaucoma. Prog Brain Res. 2008;173:511-519.
115. Parameswaran S, et al. Induced pluripotent stem cells (iPSCs) generate both retinal ganglion cells and photoreceptors: Therapeutic implications in degenerative changes in glaucoma and age-related macular degeneration. Stem Cells. 2010;28(4):695-703.
116. Dahlmann-Noor AH, Vijay S, Limb GA, Khaw PT. Strategies for optic nerve rescue and regeneration in glaucoma and other optic neuropathies. Drug Discov Today. 2010;15(7-8):287-299.
117. Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR. Local mesenchymal stem cell transplantation confers neuroprotection in experimental glaucoma. Invest Ophthalmol Vis Sci. 2010;51:2051-2059.
118. Bull ND, Irvine KA, Franklin RJ, Martin KR. Transplanted oligodendrocyte precursor cells reduce neurodegeneration in a model of glaucoma. Invest Ophthalmol Vis Sci. 2009;50(9):4244-4253.
119. Kelley MJ, Rose AY, Keller KE, Hessle H, Samples JR, Acott TS. Stem cells in the trabecular meshwork: present and future promises. Exp Eye Res. 2009;88(4):747-751.
120. Kass MA, et al. Delaying treatment of ocular hypertension: the ocular hypertension treatment study. Arch Ophthalmol. 2010;128(3):276-287.
121. Ocular Hypertension Treatment Study Group et al. Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology. 2007;114(1):10-19.
122. Leung CK, et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography a study on diagnostic agreement with Heidelberg Retinal Tomograph. Ophthalmology. 2010;117(2):267-274.
123. Schmitz-Valckenberg S, et al. Real-time in vivo imaging of retinal cell apoptosis after laser exposure. Invest Ophthalmol Vis Sci. 2008;49(6):2773-2780.
124. Suriyapperuma SP, et al. A new locus (GLC1H) for adult-onset primary open-angle glaucoma maps to the 2p15-p16 region. Arch Ophthalmol. 2007;125(1):86-92.
125. Stoilova D, Child A, Trifan OC, Crick RP, Coakes RL, Sarfarazi M. Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region. Genomics. 1996;36(1):142-150.
126. Sherwin JC, Hewitt AW, Bennett SL, Baird PN, Craig JE, Mackey DA. Primary open angle glaucoma in subjects harbouring the predicted GLC1L haplotype reveals a normotensive phenotype. Clin Experiment Ophthalmol. 2009;37(2):201-207.
127. Wirtz MK, et al. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q. Am J Hum Genet. 1997;60(2):296-304.
128. Wirtz MK, et al. GLC1F, a new primary open-angle glaucoma locus, maps to 7q35-q36. Arch Ophthalmol. 1999;117(2):237-241.
129. Trifan OC, et al. A third locus (GLC1D) for adult-onset primary open-angle glaucoma maps to the 8q23 region. Am J Ophthalmol. 1998;126(1):17-28.
130. Phillips JC, et al. A second locus for Rieger syndrome maps to chromosome 13q14. Am J Hum Genet. 1996;59(3):613-619.
131. Inagaki Y, et al. Polymorphism of beta-adrenergic receptors and susceptibility to open-angle glaucoma. Mol Vis. 2006;12:673-680.
132. Lam CY, et al. Association of apolipoprotein E polymorphisms with normal tension glaucoma in a Chinese population. J Glaucoma. 2006;15(3):218-222.
133. Fourgeux C, et al. Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxycholesterol levels. Invest Ophthalmol Vis Sci. 2009;50(12):5712-5717.
134. Kim SH, et al. Investigations on the association between normal tension glaucoma and single nucleotide polymorphisms of the endothelin-1 and endothelin receptor genes. Mol Vis. 2006;12:1016-1021.
135. Ayub H, et al. Association of eNOS and HSP70 gene polymorphisms with glaucoma in Pakistani cohorts. Mol Vis. 2010;16:18-25.
136. Tsai FJ, Lin HJ, Chen WC, Chen HY, Fan SS. Insulin-like growth factor-II gene polymorphism is associated with primary open angle glaucoma. J Clin Lab Anal. 2003;17(6):259-263.
137. Clement CI, Goldberg I, Healey PR, Graham SL. Plasma homocysteine, MTHFR gene mutation, and open-angle glaucoma. J Glaucoma. 2009;18(1):73-78.
138. Wolf C, et al. Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study. BMC Med Genet. 2009;10:91.
139. Funayama T, et al. SNPs and interaction analyses of noelin 2, myocilin, and optineurin genes in Japanese patients with open-angle glaucoma. Invest Ophthalmol Vis Sci. 2006;47(12):5368-5375.
140. Yu-Wai-Man P, et al. OPA1 increases the risk of normal but not high tension glaucoma. J Med Genet. 2010;47(2):120-125.
141. Inagaki Y, et al. Paraoxonase 1 gene polymorphisms influence clinical features of open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 2006;244(8):984-990.
142. Lin HJ, Tsai CH, Tsai FJ, Chen WC, Chen HY, Fan SS. Transporter associated with antigen processing gene 1 codon 333 and codon 637 polymorphisms are associated with primary open-angle glaucoma. Mol Diagn. 2004;8(4):245-252.
143. Shibuya E, et al. Association of Toll-like receptor 4 gene polymorphisms with normal tension glaucoma. Invest Ophthalmol Vis Sci. 2008;49(10):4453-4457.
144. Fan BJ, et al. Association of polymorphisms of tumor necrosis factor and tumor protein p53 with primary open angle glaucoma: A replication study of ten genes in a Chinese population [published online ahead of print March 31, 2010]. Invest Ophthalmol Vis Sci. doi:10.1167/iovs.09-4974.