Abstract
Proliferative vitreoretinopathy (PVR), the most common cause of failure of rhegmatogenous retinal detachment (RD) surgery, is an anomalous scarring process related to ocular inflammation. Lysyl oxidase (LOX) is a copper-dependent amine oxidase that may play important roles in ocular tissue integrity. The aim of this study was to investigate whether polymorphisms in the LOX gene were associated with susceptibility to RD and PVR. We screened the promoter region of LOX gene and tested two previously reported polymorphisms (−22 G/C and 473 G/A) in RD patients with or without PVR and healthy controls. Data showed that prevalence of the -22CC genotype and -22C allele were significantly higher in the RD cases than in the control group after adjustment for sex and age (p < 0.001 and p < 0.001, respectively). Similarly, a significant difference was observed regarding LOX 473GA genotype and 473A allele between RD patients and healthy donors after adjustment for sex and age (p = 0.005 and p = 0.012, respectively). Also, when compared to RD cases without PVR, patients who developed PVR had significantly higher numbers of -22CC genotype and -22C allele (p = 0.048 and p = 0.003, respectively). These results indicated that LOX polymorphisms were associated with increased susceptibility to RD and PVR and suggest a potential correlation between LOX and ocular inflammation.
References
Machemer, R., T.M. Aaberg, H.M. Freeman, A.R. Irvine, J.S. Lean, and R.M. Michels. 1991. An updated classification of retinal detachment with proliferative vitreoretinopathy. Am J Ophthalmol 112: 159–165.
de la Rúa, E., J.C. Pastor, I. Fernández, M.R. Sanabria, J. García-Arumí, V. Martínez-Castillo, et al. 2008. Non-complicated retinal detachment management: Variations in 4 years. Retina 1 project; report 1. Br J Ophthalmol 92: 523–525.
Miller, B., H. Miller, R. Patterson, and S.J. Ryan. 1986. Retinal wound healing. Cellular activity at the vitreoretinal interface. Arch Ophthalmol 104: 281–285.
Scott J.D. 1989. Pathogenesis of PVR with analysis of events leading to recurrent retinal detachment. In Proliferative vitreoretinopathy, eds. Heimann K and Wiedemann P. Heidelberg: Kaden.
Pastor, J.C. 1998. Proliferative vitreoretinopathy: An overview. Surv Ophthalmol 43: 3–18.
Wiedemann, P. 1992. Growth factors in retinal diseases: Proliferative vitreoretinopathy, proliferative diabetic retinopathy and retinal degeneration. Surv Ophthalmol 36: 373–384.
Zacks, D.N., Y. Han, Y. Zeng, and A. Swaroop. 2006. Activation of signaling pathways and stress-response genes in an experimental model of retinal detachment. Invest Ophthalmol Vis Sci 47: 1691–1695.
Retina Society Terminology Committee. 1983. The classification of retinal detachment with proliferative vitreoretinopathy. Ophthalmology 90: 121–125.
Lucero, H.A., and H.M. Kagan. 2006. Lysyl oxidase: An oxidative enzyme and effector of cell function. Cell Mol Life Sci 63: 2304–2316.
Ito, H., H. Akiyama, H. Iguchi, K. Iyama, M. Miyamoto, K. Ohsawa, et al. 2001. Molecular cloning and biological activity of a novel lysyl oxidase-related gene expressed in cartilage. J Biol Chem 276: 24023–24029.
Cardoso, W.V. 2001. Molecular regulation of lung development. Annu Rev Physiol 63: 471–494.
Gilad, G.M., H.M. Kagan, and V.H. Gilad. 2005. Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer’s disease brain. Neurosci Lett 376: 210–214.
Wilmarth, K.R., and J.R. Froines. 1992. In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles. J Toxicol Environ Health 37: 411–423.
Erler, J.T., K.L. Bennewith, M. Nicolau, N. Dornhofer, C. Kong, Q.T. Le, et al. 2006. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440: 1222–1226.
Erler, J.T., and A.J. Giaccia. 2006. Lysyl oxidase mediates hypoxic control of metastasis. Cancer Res 66: 10238–10241.
Li, X., W. Shi, G. Yu, L. Lin, B. Yang, J. Li, et al. 2012. Interleukin-4–590 T/C polymorphism influences the susceptibility to nonsmall cell lung cancer. DNA Cell Biol 31: 797–800.
Song, B., Y. Liu, J. Liu, X. Song, Z. Wang, M. Wang, et al. 2011. CTLA-4 +49A>G polymorphism is associated with advanced non-small cell lung cancer prognosis. Respiration 82: 439–444.
Min, C., Z. Yu, K.H. Kirsch, Y. Zhao, S.R. Vora, P.C. Trackman, et al. 2009. A loss-of-function polymorphism in the propeptide domain of the LOX gene and breast cancer. Cancer Res 69: 6685–6693.
Yoon, J.H., J.K. Park, Y.H. Kang, Y.K. Park, S.W. Nam, J.Y. Lee, et al. 2011. Lysyl oxidase G473A polymorphism is closely associated with susceptibility to gastric cancer in a South Korean population. APMIS 119: 762–768.
Oue, N., Y. Mitani, J. Motoshita, S. Matsumura, K. Yoshida, H. Kuniyasu, et al. 2006. Accumulation of DNA methylation is associated with tumor stage in gastric cancer. Cancer 106: 1250–1259.
Hollosi, P., J.K. Yakushiji, K.S. Fong, K. Csiszar, and S.F. Fong. 2009. Lysyl oxidase-like 2 promotes migration in noninvasive breast cancer cells but not in normal breast epithelial cells. Int J Cancer 125: 318–327.
Li, A.F., N. Tane, and S. Roy. 2004. Fibronectin overexpression inhibits trabecular meshwork cell monolayer permeability. Mol Vis 10: 750–757.
Chronopoulos, A., A. Tang, E. Beglova, P.C. Trackman, and S. Roy. 2010. High glucose increases lysyl oxidase expression and activity in retinal endothelial cells: Mechanism for compromised extracellular matrix barrier function. Diabetes 59: 3159–3166.
Tsuchiya, M.I., H. Okuda, Y. Takaki, M. Baba, S.I. Hirai, S. Ohno, et al. 2005. Renal cell carcinoma- and pheochromocytoma-specific altered gene expression profiles in VHL mutant clones. Oncol Rep 13: 1033–1041.
Kannan, K., N. Amariglio, G. Rechavi, J. Jakob-Hirsch, I. Kela, N. Kaminski, et al. 2001. DNA microarrays identification of primary and secondary target genes regulated by p53. Oncogene 20: 2225–2234.
Rost, T., V. Pyritz, I.O. Rathcke, T. Gorogh, A.A. Dunne, and J.A. Werner. 2003. Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas. Anticancer Res 23: 1565–1573.
Liu, Y., B. Lv, Z. He, Y. Zhou, C. Han, G. Shi, et al. 2012. Lysyl oxidase polymorphisms and susceptibility to osteosarcoma. PLoS One 7: e41610. doi:10.1371/journal.pone.0041610.
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Publication of this article was supported by grant 2011KF03 from the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
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Honghua Yu and Tao Li contributed equally to this work.
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Yu, H., Li, T., Zou, X. et al. Effects of Lysyl Oxidase Genetic Variants on the Susceptibility to Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy. Inflammation 36, 839–844 (2013). https://doi.org/10.1007/s10753-013-9610-6
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DOI: https://doi.org/10.1007/s10753-013-9610-6