Academic journal article Environmental Health Perspectives

Bone Lead Levels and Risk of Incident Primary Open-Angle Glaucoma: The VA Normative Aging Study

Academic journal article Environmental Health Perspectives

Bone Lead Levels and Risk of Incident Primary Open-Angle Glaucoma: The VA Normative Aging Study

Article excerpt

Introduction

Glaucoma accounts for approximately 8% of global blindness according to the 2010 World Health Organization report (Pascolini and Mariotti 2012). It is the second leading cause of blindness in the world after cataracts, and the leading cause of irreversible loss of vision (Pascolini and Mariotti 2012). Despite the large patient population and severe consequences, the exact etiology of glaucoma is still unclear. Based on glaucoma clinical trials, the established risk factors for glaucoma include older age, intraocular pressure, race, myopia, optic nerve susceptibility, and positive family history (Jonas et al. 2017). Other clinical risk factors, such as various systemic diseases (e.g., diabetes, hypertension, ischemic vascular diseases) and unhealthy behaviors (e.g., smoking, alcohol consumption), remain inconsistent among different studies (Cioffi and American Academy of Ophthalmology 2014; Doshi et al. 2008; Fan et al. 2004; Ko et al. 2016; Renard et al. 2013). Although there is a large population burden and severe consequence to quality of life, there is a gap in knowledge to advance our understanding beyond the established clinical risk factors for glaucoma.

In addition to clinical risk factors, genetic risk factors for glaucoma have been established through the Mendelian studies and genome-wide association studies (GWAS) (Cioffi and American Academy of Ophthalmology 2014; Mabuchi et al. 2015; Sakurada and Mabuchi 2015; Wiggs 2015; Wiggs et al. 2013). Adult-onset glaucoma occurs mostly among individuals >40 y of age. Primary open-angle glaucoma (POAG) is the major form of adult-onset glaucoma in the United States (prevalence: 1.9%) (Friedman et al. 2004). A recent heritability estimate to quantify the proportion of genetic attribution on the total phenotype variation of POAG was about 42%, which was lower than its proportion for age-related macular degeneration (AMD) (>70%) (Cuellar-Partida et al. 2016). Although the various genetic risk alleles for specific forms of glaucoma have been successfully identified by linkage and GWAS approaches, the environmental risk factors for glaucoma have proven difficult to identify.

Oxidative stress plays a role in glaucoma pathogenesis (Babizhayev 2012; Goyal et al. 2014; Majsterek et al. 2011; Zhao et al. 2016). The pathophysiology of glaucoma involves complex tissues in the anterior segment that regulate aqueous humor fluid dynamics and determine intraocular pressure and posterior segment end organ damage of the optic nerve, which was recently reviewed by Jonas et al. (2017). The complex relationships among the delicate ganglion cells that contribute to the axonal fibers of the optic nerve, the vascular supply, the glial support tissue, and the connective support tissues in the optic nerve canal as well as counter-pressure from the cerebral spinal fluid are active areas of research (Jonas et al. 2017). Within these tissues, markers of oxidative stress--such as superoxide dismutase, glutathione peroxidase, and catalase levels--are elevated in the aqueous humor of patients with POAG (Babizhayev 2012; Goyal et al. 2014; Majsterek et al. 2011). Oxidative stress can disrupt the normal function of trabecular meshwork cells, block the outflow of aqueous humor, and increase the intraocular pressure (Babizhayev 2012; Sacca et al. 2016; Zhao et al. 2016). In the posterior segment, elevated 4-hydroxy-2-nonenal adducts generated by free radicals have been detected in the glaucomatous retina cases, implying that oxidative stress plays a pathogenic role damaging the retina/optic nerve (Tezel et al. 2010).

As a key environmental source of oxidative stress, heavy metals may be an important risk factor for glaucoma. As early as 1990, a study reported higher copper levels in the aqueous humor of glaucoma patients (Akyol et al. 1990). Recent studies have also indicated a significant association between heavy metal and glaucoma. A cross-sectional analysis of the Korean National Health and Nutrition Examination Survey (KNHANES) found that higher blood mercury and lower blood manganese levels were associated with higher prevalence of glaucoma (Lin et al. …

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