June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Aspirin and its metabolite, hippuric acid, increase VEGF Expression in human retinal pigment epithelium cells
Author Affiliations & Notes
  • Johana Santa Maria
    Ophthalmology, Loyola University Chicago, Maywood, Illinois, United States
  • Maleen Cabe
    Molecular Pharmacology and Neuroscience, Loyola University Chicago, Maywood, Illinois, United States
  • Omer Iqbal
    Ophthalmology, Loyola University Chicago, Maywood, Illinois, United States
    Pathology and Laboratory Medicine, Loyola University Chicago, Maywood, Illinois, United States
  • Simon Kaja
    Molecular Pharmacology and Neuroscience, Loyola University Chicago, Maywood, Illinois, United States
    Ophthalmology, Loyola University Chicago, Maywood, Illinois, United States
  • Footnotes
    Commercial Relationships   Johana Santa Maria, None; Maleen Cabe, None; Omer Iqbal, None; Simon Kaja, Experimentica Ltd. (C), Experimentica Ltd., K&P Scientific LLC (F), Experimentica Ltd., K&P Scientific LLC (I), Experimentica Ltd., K&P Scientific LLC (P)
  • Footnotes
    Support  Illinois Society for the Prevention of Blindness (JSM, SK), NIH T35 training grant “Basic and Clinical Research Training for Medical Students” supported by the National Heart Lung and Blood Institute (NHLBI) (JSM), Dr. John P. and Therese E Mulcahy Endowed Professorship in Ophthalmology (SK), Richard A. Perritt, M.D. Charitable Foundation
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2289. doi:
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    • Get Citation

      Johana Santa Maria, Maleen Cabe, Omer Iqbal, Simon Kaja; Aspirin and its metabolite, hippuric acid, increase VEGF Expression in human retinal pigment epithelium cells. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2289.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Clinical studies have shown a positive association between aspirin use and the incidence of exudative age-related macular degeneration (AMD). The physiological mechanisms underlying this clinical association remain unknown. We hypothesize that exposure to aspirin and its metabolite, hippuric acid, disturb retinal pigmented epithelium (RPE) homeostasis by increasing VEGF-A expression in human RPE cells.

Methods : Human ARPE19 (ATCC® CRL-2302™) cells were serum-starved and exposed to either aspirin (3.25 μg/ml or 9.25 μg/ml), hippuric acid (3.25 μg/ml ) or vehicle (media + 1% fetal bovine serum) for 3 hrs. VEGF-A secretion was quantified by enzyme-linked immunosorbent assay (ELISA; R&D Systems, Minneapolis, MN).

Results : Exposure of RPE cells to aspirin (3.25 μg/ml) resulted in a 25.0 ± 4.2% increase in VEGF secretion. Similarly, hippuric acid (3.25 μg/ml) caused a 25.0 ± 4.2% increase in VEGF secretion. In contrast, a higher dose of aspirin (9.25 μg/ml) resulted only in a modest increase (9.0 ± 8.8%) of VEGF secretion. Baseline VEGF-A secretion levels were typical for ARPE19 cells (306 ± 28 pg/ml), increasing to 408 ± 36pg/ml in the presence of hippuric acid and 416 ± 29 pg/ml following aspirin (3.25 μg/ml) exposure.

Conclusions : Our data are consistent with our hypothesis that aspirin increases secretion of VEGF-A from human ARPE19 cells. Given the effect of hippuric acid, this increase is likely mediated by this primary metabolite of aspirin. Effects of aspirin metabolism on VEGF-A secretion in the RPE may contribute to the observed clinical association between aspirin use and exudative AMD.

This is a 2020 ARVO Annual Meeting abstract.

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