Background Age-related degeneration(AMD) and asthma are both diseases that are related to the activation of the complement system. The association between AMD and asthma has been debated in previous studies. The authors investigated the relationship between AMD and asthma systemically. Principal Findings The epidemiological study showed that asthma was related to choroidal neovascularization(CNV) subtype(OR = 1.721, P = 0.023). However, the meta-analysis showed there was no association between AMD and asthma. In an animal model, we found more fluoresce in leakage of CNV lesions by FA analysis and more angiogenesis by histological analysis in rats with asthma. Western blot demonstrated an elevated level of C3α-chain, C3α’-chain and VEGF. After compstatin was intravitreally injected, CNV leakage decreased according to FA analysis, with the level of C3 and VEGF protein decreasing at the same time. Significance This study first investigated the relationship between AMD and asthma systematically, and it was found that asthma could be a risk factor for the development of AMD. The study may provide a better understanding of the disease, which may advance the potential for screening asthma patients in clinical practice.
References
[1]
Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358: 2606–2617.
[2]
Bressler NM (2004) Age-related macular degeneration is the leading cause of blindness. JAMA. pp. 1900–1901.
[3]
Bora PS, Sohn JS, Cruz JMC, P Jha, Nishihori H, et al. (2005) Role of Complement and Complement Membrane Attack Complex in Laser-Induced Choroidal Neovascularization1. J Immunol 174: 491–497.
[4]
Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, et al. (2006) Drusen complement components C3a and C5apromote choroidal neovascularization. PNAS 103: 2328–2333.
[5]
Lee YL, Lee KF, Xu JS, He QY, Chiu JF, et al. (2004) The Embryotrophic Activity of Oviductal Cell-derived Complement C3b and iC3b, a Novel Function of Complement Protein in Reproduction. THE JOURNAL OF BIOLOGICAL CHEMISTRY 279: 12763–12768.
[6]
Seddon JM, Chen CA (2004) The epidemiology of age-related macular degeneration. Int Ophthalmol Clin 44:
[7]
Rakic JM (2006) Multifactorial influences on age-related macular degeneration. Bull Soc Belge Ophtalmol 301: 9–11.
[8]
Montezuma SR, Sobrin L, Seddon JM (2007) Review of genetics in age related macular degeneration. Semin Ophthalmo 22: 229–240.
[9]
Scholl HPN, Fleckenstein M, Issa PC, Keilhauer C, Holz FG, et al. (2007) An update on the genetics of age-related macular degeneration. Mol Vis 13: 196–205.
[10]
Rohrer B, Long Q, Coughlin B, Wilson RB, Huang Y, et al. (2009) A Targeted Inhibitor of the Alternative ComplementPathway Reduces Angiogenesis in a Mouse Model ofAge-Related Macular Degeneration. Investigative Ophthalmology & Visual Science 50: 3056–3064.
[11]
Xu L, Wang Y, Li Y, Wang Y, Cui T, et al. (2006) Causes of blindness and visual impairment in urban and rural areas in Beijing: the Beijing Eye Study. Ophthalmology 113: 1134.e1131–1111.
[12]
Vingerling JR, Dielemans I, Hofman A, Grobbee DE, Hijmering M, et al. (1995) The prevalence of agerelated maculopathy in the Rotterdam Study. Ophthalmology 102: 205–210.
[13]
Vinding T (1990) Visual impairment of age-related macular degeneration. An epidemiological study of 1000 aged individuals. Acta Ophthalmol (Copenh) 68: 162–167.
[14]
Ida H, Tobe T, Nambu H, Madsumura M, Uyama M, et al. (2003) RPE Cells Modulate Subretinal Neovascularization, but Do Not Cause Regression in Mice with Sustained Expression of VEGF. Investigative Ophthalmology & Visual Science 44: 5430–5438.
[15]
Mizutani N, Nabe T, Yoshino S (2009) Complement C3a Regulates Late Asthmatic Response and Airway Hyperresponsiveness in Mice. J Immunol 183: 4039–4046.
[16]
Inoue H, Mashimo Y, Funamizu M, Shimojo N, Hasegawa K, et al. (2008) Association study of the C3 gene with adult and childhood asthma. J Hum Genet 53: 728–738.
[17]
Abdel Fattah M, El Baz M, Sherif A, Adel A (2010) Complement Components (C3, C4) as Inflammatory Markers in Asthma. Indian Journal of Pediatrics Volume 77: 771–773.
[18]
Moorthy S, Cheung N, Klein R, Shahar E, Wong TY (2011) Are Lung Disease and Function Related to Age-Related Macular Degeneration? AMERICAN JOURNAL OF OPHTHALMOLOGY 151: 375–379.
[19]
Wysong A, Lee PP, Sloan FA (2009) Longitudinal Incidence of Adverse Outcomes of Age-Related Macular Degeneration. ARCH OPHTHALMOL 127: 320–327.
[20]
Klein R, Klein BK, Linton KL (1992) Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 99: 933–943.
[21]
Klein R, Knudtson MD, Klein BE (2008) Pulmonary Disease and Age-Related Macular Degeneration: The Beaver Dam Eye Study. ARCH OPHTHALMOL 126: 840–846.
[22]
Shalev V, Sror M, Goldshtein I, Kokia E, Chodick G (2011) Statin Use and the Risk of Age Related Macular Degeneration in a Large Health Organization in Israel. Ophthalmic Epidemiology 18: 83–90.
[23]
Wang JJ, Rochtchina E, Lee AJ, Chia EM, Smith W, et al. (2007) Ten-Year Incidence and Progression of Age-Related Maculopathy: The Blue Mountains Eye Study. Ophthalmology 114: 92–98.
[24]
Park KH, Fridley BL, Ryu E, Tosakulwong N, Edwards AO (2009) Complement component 3 (C3) haplotypes and risk of advanced age-related macular degeneration. Invest Ophthalmol Vis Sci 50: 3386–3393.
[25]
Francis PJ, Hamon SC, Ott J, Weleber RG, Klein ML (2009) Polymorphisms in C2, CFB and C3 are associated with progression to advanced age related macular degeneration associated with visual loss. J Med Genet 46: 300–307.
[26]
Seddon JM, Reynolds R, Maller J, Fagerness JA, Daly MJ, et al. (2009) Prediction Model for Prevalence and Incidence of Advanced Age-Related Macular Degeneration Based onGenetic, Demographic, and Environmental Variables. Investigative Ophthalmology & Visual Science, December 2003 50: 2050.
[27]
de Victoria AL, Gorham RD Jr, Bellows-Peterson ML, Ling J, Lo DD, et al. (2011) A New Generation of Potent Complement Inhibitors of the Compstatin Family. Chem Biol Drug Des 77: 431–440.
[28]
Sahu A, Morikis D, Lambris JD (2003) Compstatin, a peptide inhibitor of complement, exhibits species-specific binding to complement component C3. Molecular Immunology 39: 557–566.
[29]
Yu KD, Yang C, Fan L, Chen AX, Shao ZM (2011) RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers: evidence from a meta-analysis of 12 studies. Breast Cancer Res Trea 126: 365–371.
[30]
Chakravarthy U, Wong TY, Fletcher A, Piault E, Evans C, et al. (2010) Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol. doi:10.1186/1471–2415–10–31.
[31]
Chen SD, Wen ZH, Chang WK, Chan KH, Tsou MT, et al. (2008) Acute effect of methylprednisolone on the brain in a rat model of allergic asthma. Neuroscience Letter440: 89–91.
[32]
Werner-Klein M, G？ggel R, Westhof A, Erb KJ (2008) Development and characterisation of a novel and rapid lung eosinophil influx model in the rat. Pulmonary Pharmacology & Therapeutics 21: 648–656.
[33]
Berdugo M, Bejjani RA, Valamanesh F, Savoldelli M, Jeanny JC, et al. (2008) Evaluation of the New Photosensitizer Stakel (WST-11) for Photodynamic Choroidal Vessel Occlusion in Rabbit and Rat Eyes. Investigative Ophthalmology & Visual Science 49: 1633–1644.
[34]
Sheets KG, Zhou Y, Ertel MK, Knott EJ, Regan CE , et al. (2010) Neuroprotectin D1 Attenuates Laser-induced ChoroidalNeovascularization in Mouse. Molecular Vision 16: 320–329.
[35]
Kim C, Yu HG, Sohn J (2010) The Anti-angiogenic Effect of Chlorogenic Acid on Choroidal Neovascularization. Korean J Ophthalmol 24(3): 163–168.
[36]
Lyzogubov VV, Tytarenko RG, Liu J, Bora NS, Bora PS (2011) Polyethylene Glycol (PEG)-induced Mouse Model of Choroidal Neovascularization. THE JOURNAL OF BIOLOGICAL CHEMISTRY 286: 16229–16237.
[37]
Zhou P, Fan L, Yu KD, Zhao MW, Li XX (2011) Toll-like receptor 3 C1234T may protect againstgeographic atrophy through decreased dsRNAbinding capacity. The FASEB Journal. doi:10.1096/fj.11–189258.
