Urinary Isoprostane Levels and Age-Related Macular Degeneration

Abstract

PURPOSE. Oxidative stress, characterized by an excessive production of reactive oxygen intermediates has been suggested to play a role in the pathogenesis of age-related macular degeneration (AMD). We examined the association of urinary F2-isoprostanes (F2-IsoPs), a marker of lipid peroxidation and the most reliable marker of oxidative damage with AMD. METHODS.We included 238 adults with AMD and 390 age-and sex-matched controls without AMD who participated in a population-based cross-sectional study in Singapore (Singapore Chinese Eye Study, 2009-2011. AMD was graded from retinal photographs using the Wisconsin Age-Related Maculopathy Grading System. Urinary-free F2-IsoPs (pmol/mmol of creatinine) were measured by gas chromatography mass spectrometry (GC-MS). The association between F2-IsoPs and AMD was examined using unconditional logistic regression models adjusted for potential confounders including smoking, body mass index (BMI), blood pressure, total and high-density lipoprotein cholesterol, and history of cardiovascular disease. RESULTS.Higher levels of F2-IsoPs were associated with AMD independent of potential confounders. Compared to quartile 1 (Q1) of F2-IsoPs, the multivariable odds ratio (95% confidence interval) of AMD in quartiles 2, 3, and 4 were 2.05 (1.26-3.32), 1.80 (1.10-2.94), and 1.76 (1.06-2.94), respectively. In subgroup analyses comparing Q4 to Q1, this association was stronger in women, those with BMI less than 25 kg/m 2 and those with hypertension, but no significant interaction was found (P interaction > 0.1 for each strata).CONCLUSIONS. Higher levels of urinary F2-IsoPs levels were associated with AMD independent of potential confounders in Chinese adults.Keywords: age-related macular degeneration, Asians, isoprostane, oxidative stress A ge-related macular degeneration (AMD) is a leading cause of irreversible blindness in older adults worldwide.1,2 Globally, 170 million adults have AMD, exerting a significant socioeconomic burden on healthcare systems.2,3 Despite significant research over decades, the pathogenesis of AMD is still not clear, and robust systemic biomarkers of AMD have not been identified yet. 4 Oxidative stress, characterized by an imbalance between excessive generation of reactive oxygen species (ROS) and their degradation by antioxidants, has recently been proposed to play a significant role in the pathogenesis of AMD. [5][6][7] With advancing age, the retina becomes more susceptible to oxidative stress and damage to the retinal pigment epithelium (RPE) occurs early in the natural history of AMD.8 At physiological concentrations, ROS are involved in cell signaling and regulation of immune responses. 9 However, disproportionate levels of ROS with concurrent impairment of enzymatic and nonenzymatic antioxidants damage cellular proteins, membrane lipids, and DNA that eventually lead to tissue injury, cellular death 10 resulting in accumulation of detrimental products including intracellular lipofuscin, and extracellular drusen. 6Oxidation of membrane lipids or lipid pero...

Increase in omega-6 and decrease in omega-3 polyunsaturated fatty acid oxidation elevates the risk of exudative AMD development in adults with Chinese diet

“…In addition, elevated urinary 15-F 2t -IsoP and its downstream metabolite 2,3-dinor-5,6-dihydro-15-F 2t -IsoP were also observed. These findings are consistent with other report but provide additional details on changes in omega-6 PUFA metabolism of AMD [33]. Notably, elevation of urinary 11-HETE strongly increased the odds of AMD development.…”

A serum metabolomics study of patients with nAMD in response to anti-VEGF therapy

“…Demographic and medical history. Baseline socio-demographic and medical history was collected using an interviewer-administered questionnaire which was previously validated [52][53][54] . Data included information on participants' lifestyle factors, history of smoking, current medications, systemic medical and surgical history.…”

Oxidative stress, aging, and diseases

“… 85 Moreover, a recent interesting French study analyzed the relationships between the accumulation of AGEs, assessed by skin autofluorescence (AF), and frailty in 423 older community-dwellers aged ≥75 years, showing that the accumulation of AGEs was not associated with prevalent or incident frailty but with the 4-year risk of exhaustion and low energy expenditure. 87 Nevertheless, increased levels of AGEs are associated with sarcopenia in elderly subjects, 86 while decreased levels of RAGEs are markers of severity and accelerated aging in COPD patients; 43 oxLDL levels, as described in the section “Oxidative stress and CVDs”, correlate with arterial stiffness and athero-genesis in the elderly, not predicting mortality; 26 , 27 -HNE levels are elevated in elderly subjects with NDs (ie, AD, PD, HD, and ALS) 88 and sarcopenia; 89 F 2 -isoprostanes urinary levels are increased in several diseases frequently diagnosed in elderly patients, such as depression, 90 age-related macular degeneration (AMD), 91 AD and HD, 92 COPD, 41 and CKD, where it correlates with disease progression; 79 MDA increased plasma levels correlate with low cognitive performance in institutionalized elderly subjects; 54 its levels increase in elderly subjects with T2D but not with IGT 38 and in CKD, where its levels are inversely related to glomerular filtration rate (GFR) and positively correlated with uremic toxins and severity of glomerulosclerosis; 79 NT levels are used as biomarkers of COPD 41 and sarcopenia 93 in elderly subjects, and high levels are associated with vascular endothelial dysfunction with aging; 30 , 31 DNA modifications, 8oxodG and 7,8-dihydro-8-oxoguanosine (8oxoGuo), are excreted into the urine and measured with enzyme-linked immunosorbent assay. Both are markers of inflammation and carcinogenesis in the elderly.…”

“…F 2 -isoprostanes urinary levels are increased in several diseases frequently diagnosed in elderly patients, such as depression, 90 age-related macular degeneration (AMD), 91 AD and HD, 92 COPD, 41 and CKD, where it correlates with disease progression; 79 …”