Associations of Environmental Risk Factors with Age-Related Cataract and Glaucoma

environmental risk factors;age-related cataract;open-angle glaucoma;bone lead;dietary pattern;Public Health;Health Sciences;Epidemiological Science

Wang, WeiyeMukherjee, Bhramar ;

University of Michigan

关键词: environmental risk factors;    age-related cataract;    open-angle glaucoma;    bone lead;    dietary pattern;    Public Health;    Health Sciences;    Epidemiological Science;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/147654/weiyew_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Cataract and Glaucoma are two leading causes of visual impairment and blindness, showing an increasing prevalence with age. However, in spite of this significance, the etiology of age-related cataract (ARC) or glaucoma is still unclear. Previous studies implied that although genes play a role in the development of ARC and glaucoma, knowledge regarding the influence of environmental factors is also emerging. Much evidence suggests that oxidative stress increases the risk of ARC and glaucoma, while heavy metal exposure, a well-known source of increased oxidative stress, may be linked to the risk of disease. However, for glaucoma, previous epidemiological studies on heavy metals were mainly conducted in Asian populations and were cross-sectional, raising concerns related to causal inferences and problems of reverse causality. Furthermore, lead exposure measurements were based on blood or hair lead levels, reflecting relatively recent doses, which limits inferences regarding chronic effects of cumulative exposure. For cataract, studies on the association of environmental pollutants other than heavy metals with ARC were very limited. We thus examined the following three aims: 1) the association between bone lead levels measured via K x-ray fluorescence and incident primary open-angle glaucoma (POAG); 2) effect modification by dietary patterns and dietary vitamin intake in the association between bone lead levels and incident POAG; and 3) a two-stage environment-wide association study (EWAS) to discover potential environmental risk factors for cataract surgery. Aims 1 and 2 were conducted using data from the Normative Aging Study, a prospective cohort study established by the United States Department of Veterans Affairs. Aim 3 utilized data from the National Health and Nutrition Examination Survey (NHANES), a national population-based public dataset established by the United States Centers for Disease Control and Prevention. We found that bone lead may be an important risk factor of POAG. A 10-fold increase in patella lead level was associated with more than 5-fold higher risk of POAG during 15 years of follow-up. Further analysis on effect modification by dietary pattern suggests that people who had high adherence to prudent dietary pattern, which contains plentiful legumes, vegetables, seafood, onions, tomatoes, fruits and poultry, were less susceptible to the toxicity of patella lead on the risk of POAG. For cataract, we found that urinary heavy metals (cadmium, cobalt and tungsten), and serum PCBs 44 and 49, were positively associated with cataract surgery by using the conventional EWAS approach. We further identified urinary mono-(3-carboxypropyl) phthalate and two VOCs (urinary N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine and urinary N-acetyl-S- (3-hydroxypropyl)-L-cysteine) as potential risk factors for cataract via weighted EWAS approach accounting for biological half-lives of pollutants. This dissertation revealed the effects of multiple unrecognized environmental risk factors for glaucoma and cataract. Our research can help better understand the role of environmental risk factors in the pathogenesis of ARC and POAG, providing new ideas for interventions regarding these two important ocular diseases, and ultimately decrease the global burden of visual impairment and blindness effectively.