Abstract
Purpose: An estimated 19.3% of adults, especially the elderly in the United States regularly use Aspirin for cardioprotection. Recently, multiple cohort studies have concluded that regular aspirin use for 10-15 years was associated with a statistically significant increase in the risk of incident age-related and neovascular acute macular degeneration. It has been hypothesized that aspirin or its metabolites induce the expression of vascular endothelial growth factor (VEGF). Materials & Methods: Retinal pigment epithelial cells, ARPE-19 (ATCC ® CRL-2302™) were cultured. The cells were grown to achieve 95% confluence and then the media was changed. Cells cultured under blue light, red light, or darkness were subjected to a challenge with high dose aspirin (0.925 mg/dL), low dose aspirin (0.325 mg/dL), or hippuric acid (0.325 mg/dL). Light was generated using 2 red or blue LEDs powered by 3v CR2032 batteries. The 24-well plate was incubated with or without drugs in blue light, red light or darkness at 37C for 16 hours. The supernatants were harvested, and VEGF was quantified. One-way ANOVA using Dunnett’s multiple comparison test was performed to analyze statistical signifi cance. Results: Cells exposed to blue light or darkness and hippuric acid showed a statistically significant increase in VEGF secre tion (P=0.0012). However, cells exposed to red light with hippuric acid challenge showed no significant difference from the mean of cells exposed to darkness and sham control. Conclusions: Retinal pigment epithelial cells challenged with oxidative stress provided by blue light or darkness in the presence of hippuric acid increased VEGF secretion, suggesting a possible cause for neovascularization in age-related macular degeneration. RPE cells exposed to red light, known to abrogate oxidative stress, had decreased levels of VEGF induction by hippuric acid.
Highlights
Age-related macular degeneration (AMD) is the leading cause of adult eye disease among industrialized nations, in the elderly [1]
Cells exposed to blue light or darkness and hippuric acid showed a statistically significant increase in Vascular Endothelial Growth Factor (VEGF) secretion (P=0.0012) using an ordinary 1 way ANOVA
Under the influence of blue light, hippuric acid expressed higher levels of VEGF measuring 114.7 ± 3.3 pg/ml compared to the dark sham control value of 105.79 ± 8.4 pg/ml (P=0.0012), while the low and high dose aspirin did not show any significant change. These results clearly show that hippuric acid can induce increased VEGF expression under the influence of blue light when compared to darkness alone; not statistically significant, there was a trend demonstrating that cells exposed to hippuric acid and blue light had increased levels of VEGF expression when compared to cells exposed to blue light alone, low dose aspirin, and high dose aspirin
Summary
Age-related macular degeneration (AMD) is the leading cause of adult eye disease among industrialized nations, in the elderly [1]. The US, Canada, and Cuba spend approximately US$98 Billion in direct healthcare costs for visual impairment due to AMD. The global estimate on AMD healthcare spending is US$255 billion [2]. AMD is a degenerative disease of the central portion of the retina, known as the macula, which results in loss of central vision. Depending on the progression of the disease, AMD is either characterized as dry type or wet type. The pathogenesis is currently poorly understood; ischemia and oxidative stress are believed to be the key factors involved. This hypoxia state results in the release of factors such as Vascular Endothelial Growth Factor (VEGF), and inflammatory signals, which help the growth of new and ab-
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