烟草烟雾与老年性黄斑变性_Chinese Journal of Ocular Fundus Diseases

Authors：

张营春 ,  赵博军

250021 济南, 山东大学附属省立医院眼科中心;

Corresponding author：

赵博军, Email: zhaobojun@hotmail.com

Keywords：

黄斑变性/病因学; 烟草对健康的危害; 尼古丁/副作用; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2014.03.029

Video：

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老年性黄斑变性(AMD)与年龄、营养、免疫、烟草烟雾等因素有关。烟草烟雾可促进脉络膜新生血管(CNV)形成,诱发AMD。烟草烟雾中的主要生物碱尼古丁通过与视网膜色素上皮细胞中烟碱胆碱受体结合从而影响血浆中血管内皮生长因子与色素上皮衍生因子的比率;收缩视网膜血管,导致缺血缺氧;烟草烟雾中的自由基或间接消耗抗氧化剂诱发氧化应激及苯并芘对视网膜的毒性作用等。在预防CNV形成、控制AMD发生中,烟草烟雾是为数不多的可确定且可预防的环境因素。充分认识吸烟与CNV以及AMD的关系,对于AMD的早期预防、探索新的治疗途径有着重要的意义。

Citation： 张营春, 赵博军. 烟草烟雾与老年性黄斑变性. Chinese Journal of Ocular Fundus Diseases, 2014, 30(3): 325-328. doi: 10.3760/cma.j.issn.1005-1015.2014.03.029 Copy

1.	Thornton J, Edwards R, Mitchell P, et al. Smoking and age-related macular degeneration: a review of association[J]. Eye (Lond),2005,19:935-944.
2.	Klein R, Knudtson MD, Cruickshanks KJ, et al. Further observations on the association between smoking and the long-term incidence and progression of age-related macular degeneration: the Beaver Dam Eye Study[J]. Arch Ophthalmol,2008,126:115-121.
3.	Pons M, Marin-Castaño ME. Nicotine increases the VEGF/PEDF ratio in retinal pigment epithelium: a possible mechanism for CNV in passive smokers with AMD[J]. Invest Ophthalmol Vis Sci,2011,52:3842-3853.
4.	Gundogan FC, Erdurman C, Durukan AH, et al. Acute effects of cigeratte smoking on multifocal electroretinogram[J]. Clin Exp Ophthalmol,2007,35:32-37.
5.	Fujihara M, Nagai N, Sussan TE,et al. Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice[J/OL]. PLoS One,2008,3:E3119[2013-03-25]. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003119.
6.	Sharma A, Neekhra A, Gramajo AL, et al. Effects of benzo(e)pyrene, a toxic component of cigarette smoke, on human retinal pigment epithelial cells in vitro[J]. Invest Ophthalmol Vis Sci,2008,49:5111-5117.
7.	Suñer IJ, Espinosa-Heidmann DG, Marin-Castano ME, et al. Nicotine increases size and severity of experimental choroidal neovascularization[J]. Invest Ophthalmol Vis Sci,2004,45:311-317.
8.	Khan JC, Thurlby DA, Shahid H, et al. Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation[J]. Br J Ophthalmol, 2006,90:75-80.
9.	Chakravarthy U, Augood C, Bentham GC, et al. Cigarette smoking and age-related macular degeneration in the EUREYE Study[J]. Ophthalmology,2007,114:1157-1163.
10.	田君,方凯,秦雪英,等.年龄相关性黄斑变性危险因素的病例对照研究[J].北京大学学报(医学版),2012,44:588-593.
11.	Klein R, Klein BE, Marino EK, et al. Early age-related maculopathy in the cardiovascular health study[J]. Ophthalmology,2003,110:25-33.
12.	Mitchell P, Wang JJ, Smith W, et al. Smoking and the 5-year incidence of age-related maculopathy: the Blue Mountains Eye Study[J]. Arch Ophthalmol,2002,120:1357-1363.
13.	Tomany SC, Wang HJ, Van Leeuwen R, et al. Risk factors for incident age-related macular degeneration: pooled findings from 3 continents[J].Ophthalmology,2003,111:1280-1287.
14.	Ohno-Matsui K, Morita I, Tombran-Tink J, et al. Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF[J]. J Cell Physiol, 2001,189:323-333.
15.	Kwak N, Okamoto N, Wood JM, et al. VEGF is major stimulator in model of choroidal neovascularization[J]. Invest Ophthalmol Vis Sci,2000,41:3158-3164.
16.	Zhao BJ, Cai J, Boulton M. Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2[J]. Microvasc Res,2004,68:239-246.
17.	Zhao B, Ma A, Cai J, et al. VEGF-A regulates the expression of VEGF-C in human retinal pigment epithelial cells[J]. Br J Ophthalmol, 2006,90:1052-1059.
18.	Zhao BJ, Smith G, Cai J, et al. Vascular endothelial growth factor C promotes survival of retinal vascular endothelial cells via vascular endothelial growth factor receptor-2[J]. Br J Ophthalmol, 2007,91:538-545.
19.	Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors[J]. Nat Med,2003,9:669-676.
20.	Tombran-Tink J, Barnstable CJ. Therapeutic prospects for PEDF: more than a promising angiogenesis inhibitor[J]. Trends Mol Med,2003,9:244-250.
21.	Bouck N. PEDF: anti-angiogenic guardian of ocular function[J]. Trends Mol Med,2002,8:330-334.
22.	Ambati J, Ambati BK, Yoo SH, et al. Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies[J]. Surv Ophthalmol,2003,48:257-293.
23.	Tong JP, Yao YF. Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions[J]. Clin Biochem,2006,39:267-276.
24.	Bhutto IA, McLeod DS, Hasegawa T, et al. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration[J]. Exp Eye Res,2006,82:99-110.
25.	Ohno-Matsui K, Yoshida T, Uetama T, et al. Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells[J]. Biochem Biophys Res Commun,2003,303:962-967.
26.	Tari SR, Youssif M, Samson CM,et al. Polychromatic angiography for the assessment of VEGF-induced BRB dysfunction in the rabbit retina[J]. Invest Ophthalmol Vis Sci,2013,54:5550-5558.
27.	Ross RJ, Verma V, Rosenberg KI, et al. Genetic markers and biomarkers for age-related macular degeneration[J]. Expert Rev Ophthalmol,2007,2:443-457.
28.	Snellen ELM, Verbeek ALM, van den Hoogen GWP, et al.Neovascular age-related macular degeneration and its relationship to antioxidant intake[J]. Acta Ophthalmol Scand,2002,80:368-371.
29.	Blaauwgeers HG, Holtkamp GH, Rutten H, et al.Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris: evidence for a trophic paracrine relation[J]. Am J Pathol,1999,155:421-428.
30.	赵炜,王雨生,张瑞,等.p42/p44 MAPK信号转导通路在缺氧诱导的人视网膜色素上皮细胞VEGF表达中的作用[J].眼科新进展,2005,25:109-112.
31.	Gao GQ, Li Y, Gee S, et al. Down-regulation of vascular endothelial growth factor and up-regulation of pigment epithelium-derived factor: a possible mechanism for the anti-angiogenic activity of plasminogen kringle 5[J]. J Biol Chem,2002,277:9492-9497.
32.	Nilsson SE. From basic to clinical research: a journey with the retina, the retinal pigment epithelium, the cornea, age-related macular degeneration and hereditary degenerations, as seen in the rear view mirror[J]. Acta Ophthalmol Scand,2006,84:452-465.
33.	Mazure NM, Brahimi-Horn MC, Pouyssegur J. Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis[J]. Curr Pharm Des,2003,9:531-541.
34.	Schlingemann RO. Role of growth factors and the wound healing response in age-related macular degeneration[J]. Graefe's Arch Clin Exp Ophthalmol,2004,242:91-101.
35.	Evereklioglu C, Er H, Doganay S, et al. Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration[J]. Doc Ophthalmol,2003,106:129-136.
36.	Jiang S, Moriarty-Craige SE, Orr M, et al. Oxidant-induced apoptosis in human retinal pigment epithelial cells: dependence on extracellular redox state[J].Invest Ophthalmol Vis Sci,2005,46:1054-1061.
37.	Roybal CN, Hunsaker LA, Barbash O, et al. The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism[J]. J Biol Chem,2005,280:20331-20339.
38.	Bertram KM, Baglole CJ, Phipps RP, et al. Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration[J]. Am J Physiol Cell Physiol,2009,297:1200-1210.
39.	Wang AL, Lukas TJ, Yuan M, et al. Changes in retinal pigment epithelium related to cigarette smoke: possible relevance to smoking as a risk factor for age-related macular degeneration[J/OL]. PLoS One,2009,4:E5304[2013-03-25]. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005304.
40.	Wang AL, Neufeld AH. Smoking mice: a potential model for studying accumulation of drusen-like material on Bruch's membrane[J]. Vision Res,2010,50:638-642.
41.	Klein R, Klein BE, Tomany SC et al. The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study[J]. Ophthalmology,2003,110:636-643.
42.	Solberg Y, Rosner M, Belkin M. The association between cigarrette smoking and ocular disease[J]. Surv Ophthalmol,1998,42:535-547.
43.	Yamagishi S, Matsui T, Nakamura K, et al. Pigment-epithelium-derived factor (PEDF) inhibits angiotensin-Ⅱ-induced vascular endothelial growth factor (VEGF) expression in MOLT-3 T cells through anti-oxidative properties[J]. Microvasc Res,2006,71:222-226.
44.	Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease[J]. J Am Coll Cardiol,2004,43:1731-1737.
45.	Friedman E. Update of the vascular model of AMD[J]. Br J Ophthalmol, 2004,88:161-163.

1. Thornton J, Edwards R, Mitchell P, et al. Smoking and age-related macular degeneration: a review of association[J]. Eye (Lond),2005,19:935-944.
2. Klein R, Knudtson MD, Cruickshanks KJ, et al. Further observations on the association between smoking and the long-term incidence and progression of age-related macular degeneration: the Beaver Dam Eye Study[J]. Arch Ophthalmol,2008,126:115-121.
3. Pons M, Marin-Castaño ME. Nicotine increases the VEGF/PEDF ratio in retinal pigment epithelium: a possible mechanism for CNV in passive smokers with AMD[J]. Invest Ophthalmol Vis Sci,2011,52:3842-3853.
4. Gundogan FC, Erdurman C, Durukan AH, et al. Acute effects of cigeratte smoking on multifocal electroretinogram[J]. Clin Exp Ophthalmol,2007,35:32-37.
5. Fujihara M, Nagai N, Sussan TE,et al. Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice[J/OL]. PLoS One,2008,3:E3119[2013-03-25]. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003119.
6. Sharma A, Neekhra A, Gramajo AL, et al. Effects of benzo(e)pyrene, a toxic component of cigarette smoke, on human retinal pigment epithelial cells in vitro[J]. Invest Ophthalmol Vis Sci,2008,49:5111-5117.
7. Suñer IJ, Espinosa-Heidmann DG, Marin-Castano ME, et al. Nicotine increases size and severity of experimental choroidal neovascularization[J]. Invest Ophthalmol Vis Sci,2004,45:311-317.
8. Khan JC, Thurlby DA, Shahid H, et al. Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularisation[J]. Br J Ophthalmol, 2006,90:75-80.
9. Chakravarthy U, Augood C, Bentham GC, et al. Cigarette smoking and age-related macular degeneration in the EUREYE Study[J]. Ophthalmology,2007,114:1157-1163.
10. 田君,方凯,秦雪英,等.年龄相关性黄斑变性危险因素的病例对照研究[J].北京大学学报(医学版),2012,44:588-593.
11. Klein R, Klein BE, Marino EK, et al. Early age-related maculopathy in the cardiovascular health study[J]. Ophthalmology,2003,110:25-33.
12. Mitchell P, Wang JJ, Smith W, et al. Smoking and the 5-year incidence of age-related maculopathy: the Blue Mountains Eye Study[J]. Arch Ophthalmol,2002,120:1357-1363.
13. Tomany SC, Wang HJ, Van Leeuwen R, et al. Risk factors for incident age-related macular degeneration: pooled findings from 3 continents[J].Ophthalmology,2003,111:1280-1287.
14. Ohno-Matsui K, Morita I, Tombran-Tink J, et al. Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF[J]. J Cell Physiol, 2001,189:323-333.
15. Kwak N, Okamoto N, Wood JM, et al. VEGF is major stimulator in model of choroidal neovascularization[J]. Invest Ophthalmol Vis Sci,2000,41:3158-3164.
16. Zhao BJ, Cai J, Boulton M. Expression of placenta growth factor is regulated by both VEGF and hyperglycaemia via VEGFR-2[J]. Microvasc Res,2004,68:239-246.
17. Zhao B, Ma A, Cai J, et al. VEGF-A regulates the expression of VEGF-C in human retinal pigment epithelial cells[J]. Br J Ophthalmol, 2006,90:1052-1059.
18. Zhao BJ, Smith G, Cai J, et al. Vascular endothelial growth factor C promotes survival of retinal vascular endothelial cells via vascular endothelial growth factor receptor-2[J]. Br J Ophthalmol, 2007,91:538-545.
19. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors[J]. Nat Med,2003,9:669-676.
20. Tombran-Tink J, Barnstable CJ. Therapeutic prospects for PEDF: more than a promising angiogenesis inhibitor[J]. Trends Mol Med,2003,9:244-250.
21. Bouck N. PEDF: anti-angiogenic guardian of ocular function[J]. Trends Mol Med,2002,8:330-334.
22. Ambati J, Ambati BK, Yoo SH, et al. Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies[J]. Surv Ophthalmol,2003,48:257-293.
23. Tong JP, Yao YF. Contribution of VEGF and PEDF to choroidal angiogenesis: a need for balanced expressions[J]. Clin Biochem,2006,39:267-276.
24. Bhutto IA, McLeod DS, Hasegawa T, et al. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration[J]. Exp Eye Res,2006,82:99-110.
25. Ohno-Matsui K, Yoshida T, Uetama T, et al. Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells[J]. Biochem Biophys Res Commun,2003,303:962-967.
26. Tari SR, Youssif M, Samson CM,et al. Polychromatic angiography for the assessment of VEGF-induced BRB dysfunction in the rabbit retina[J]. Invest Ophthalmol Vis Sci,2013,54:5550-5558.
27. Ross RJ, Verma V, Rosenberg KI, et al. Genetic markers and biomarkers for age-related macular degeneration[J]. Expert Rev Ophthalmol,2007,2:443-457.
28. Snellen ELM, Verbeek ALM, van den Hoogen GWP, et al.Neovascular age-related macular degeneration and its relationship to antioxidant intake[J]. Acta Ophthalmol Scand,2002,80:368-371.
29. Blaauwgeers HG, Holtkamp GH, Rutten H, et al.Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris: evidence for a trophic paracrine relation[J]. Am J Pathol,1999,155:421-428.
30. 赵炜,王雨生,张瑞,等.p42/p44 MAPK信号转导通路在缺氧诱导的人视网膜色素上皮细胞VEGF表达中的作用[J].眼科新进展,2005,25:109-112.
31. Gao GQ, Li Y, Gee S, et al. Down-regulation of vascular endothelial growth factor and up-regulation of pigment epithelium-derived factor: a possible mechanism for the anti-angiogenic activity of plasminogen kringle 5[J]. J Biol Chem,2002,277:9492-9497.
32. Nilsson SE. From basic to clinical research: a journey with the retina, the retinal pigment epithelium, the cornea, age-related macular degeneration and hereditary degenerations, as seen in the rear view mirror[J]. Acta Ophthalmol Scand,2006,84:452-465.
33. Mazure NM, Brahimi-Horn MC, Pouyssegur J. Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis[J]. Curr Pharm Des,2003,9:531-541.
34. Schlingemann RO. Role of growth factors and the wound healing response in age-related macular degeneration[J]. Graefe's Arch Clin Exp Ophthalmol,2004,242:91-101.
35. Evereklioglu C, Er H, Doganay S, et al. Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration[J]. Doc Ophthalmol,2003,106:129-136.
36. Jiang S, Moriarty-Craige SE, Orr M, et al. Oxidant-induced apoptosis in human retinal pigment epithelial cells: dependence on extracellular redox state[J].Invest Ophthalmol Vis Sci,2005,46:1054-1061.
37. Roybal CN, Hunsaker LA, Barbash O, et al. The oxidative stressor arsenite activates vascular endothelial growth factor mRNA transcription by an ATF4-dependent mechanism[J]. J Biol Chem,2005,280:20331-20339.
38. Bertram KM, Baglole CJ, Phipps RP, et al. Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration[J]. Am J Physiol Cell Physiol,2009,297:1200-1210.
39. Wang AL, Lukas TJ, Yuan M, et al. Changes in retinal pigment epithelium related to cigarette smoke: possible relevance to smoking as a risk factor for age-related macular degeneration[J/OL]. PLoS One,2009,4:E5304[2013-03-25]. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005304.
40. Wang AL, Neufeld AH. Smoking mice: a potential model for studying accumulation of drusen-like material on Bruch's membrane[J]. Vision Res,2010,50:638-642.
41. Klein R, Klein BE, Tomany SC et al. The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study[J]. Ophthalmology,2003,110:636-643.
42. Solberg Y, Rosner M, Belkin M. The association between cigarrette smoking and ocular disease[J]. Surv Ophthalmol,1998,42:535-547.
43. Yamagishi S, Matsui T, Nakamura K, et al. Pigment-epithelium-derived factor (PEDF) inhibits angiotensin-Ⅱ-induced vascular endothelial growth factor (VEGF) expression in MOLT-3 T cells through anti-oxidative properties[J]. Microvasc Res,2006,71:222-226.
44. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease[J]. J Am Coll Cardiol,2004,43:1731-1737.
45. Friedman E. Update of the vascular model of AMD[J]. Br J Ophthalmol, 2004,88:161-163.

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烟草烟雾与老年性黄斑变性

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