June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The clot may thicken in primary open angle glaucoma
Author Affiliations & Notes
  • Michael Giovingo
    Ophthalmology, John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, United States
  • Kevin Carey
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Indre Bielskus
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Michael David Miazga
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Nicholas Maxwell Pfahler
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • John R Samples
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Paul A Knepper
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
    Ophthalmology, Northwestern University, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Michael Giovingo, None; Kevin Carey, None; Indre Bielskus, None; Michael Miazga, None; Nicholas Pfahler, None; John Samples, None; Paul Knepper, Testog, Inc. (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4597. doi:
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    • Get Citation

      Michael Giovingo, Kevin Carey, Indre Bielskus, Michael David Miazga, Nicholas Maxwell Pfahler, John R Samples, Paul A Knepper; The clot may thicken in primary open angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4597.

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

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Abstract

Purpose : The cause of primary open angle glaucoma (POAG) is unknown. Recently, a multiple hit theory (Glaucoma Research and Clinical Advances: 2016 to 2018) posits three targets for POAG pathogenesis: microvascular insults to (1) ciliary body (CB) capillaries leading to trabecular meshwork cell death, (2) choroid plexus (CP) capillaries leading to decreased cerebrospinal fluid production and an increased translaminar pressure gradient, and (3) lamina cribosa capillaries leading to optic nerve axon loss. Although the cause(s) of these microvascular insults are unknown, one key factor may be the role of vascular endothelial growth factor receptor (VEGFR2) in maintaining the fenestrated capillaries. The seminal work of D’Amore (IOVS;2012) demonstrated that VEGF neutralizing antibodies lead to damaged CB and CP. The purpose of the present study is to test the effects of the reported VEGF inhibitor β-amyloid (Aβ) 1-42 on platelet viscosity.

Methods : Blood samples were obtained from control (n=3) and POAG (n=3) patients after informed consent and International Review Board approval. Platelet rich plasma (PRP) was isolated by centrifugation at 300 xg for 30 min and challenged with graded amounts of thrombin (Sigma-Aldrich) to determine the lowest concentration of thrombin without a fibrin clot. PRP was treated with graded amounts of thrombin and Aβ (1-42) (Sigma) with and without the presence of 1μM amounts of selected toll-4 inhibitors—resveratrol (R), quercetin (Q), and a μ-opiate antagonist (N)—to prevent increases in viscosity and fibrin clot formation. PRP was subjected to a low shear rate of 50 seconds-1 for 6 minutes at 37°C using a cone-plate rheometer (Brookfield).

Results : PRP treated with both Aβ and thrombin produced a seven-fold increase in viscosity when compared to thrombin or Aβ alone. This apparent synergism is present in both controls and POAG (p=0.002), as shown in Table 1. Treatment with a 1μM dose of RQN eliminated the Aβ-thrombin induced fibrin clots in both controls (p=0.04) and POAG (p=0.04).

Conclusions : Aβ 1-42 acts synergistically with thrombin to increase viscosity at a low shear rate. Notably, the toll-4 antagonists RQN prevented the Aβ synergism. The clinical implications of this finding include the increased likelihood of microvascular disease whenever shear rate is low, e.g., low blood pressure, sleep apnea, and migraine.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

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