September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Novel anti-platelet compounds to protect collagen activated platelets via GPVI: Implications for microvascular disease in POAG
Author Affiliations & Notes
  • Indre Bielskus
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Mit Patel
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Sean Forte
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • William Norkett
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Paulius Kuprys
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Kevin Carey
    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   Indre Bielskus, None; Mit Patel, None; Sean Forte, None; William Norkett, None; Paulius Kuprys, None; Kevin Carey, None; Paul Knepper, Testog Inc (P)
  • Footnotes
    Support  BrightFocus Foundation Grant G2011-047, National Eye Institute Grant P30EY01792
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2549. doi:
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      Indre Bielskus, Mit Patel, Sean Forte, William Norkett, Paulius Kuprys, Kevin Carey, Paul A Knepper; Novel anti-platelet compounds to protect collagen activated platelets via GPVI: Implications for microvascular disease in POAG. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2549.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Recently, microvascular disease has been proposed as a possible explanation for the cause of POAG. Our laboratory has observed non-ocular microvascular changes and an increased number of prothrombogenic superactivated platelets (SAPs) in patients with POAG. Glycoprotein VI (GPVI) acts as a collagen receptor on platelets, and plays an integral role in platelet aggregation and thrombus formation upon activation. In this study, we examined the role of GPVI in the platelet activation process, and its response to varying doses of resveratrol, quercetin, and naltrexone.

Methods : Whole blood was collected via venipuncture from control subjects, anticoagulated with acid citrate dextrose, and centrifuged to isolate the platelet rich plasma (PRP). The PRP was washed twice with buffered saline glucose citrate solution (BSGC), and the platelets were resuspended in BSGC. Platelets were preincubated with medium (5 μM resveratrol, 5 μM quercetin, 10 μM naltrexone), and high (10 μM resveratrol, 10 μM quercetin, 50 μM naltrexone) doses of drugs, and activated with thrombin and convulxin for 3, 7, and 20 minutes. The platelets were lysed with cell lysis buffer, and the lysate and supernatant were examined for the presence of GPVI via western blot analysis. Results of the western blots were analyzed using densitometry. A two-tailed t-test was used to determine statistical significance.

Results : GPVI ectodomain shedding was reduced at a high dose of resveratrol, quercetin, and naltrexone. Compared to controls, the high dose of drugs showed a 6.8%, 23.3%, and 33% decrease of GPVI in the supernatant at time points 3, 7, and 20 minutes, respectively (p<0.02). Additionally, in comparing the controls to the lysates, the high dose showed a 4.6% decrease, a 37.6% increase and 28% increase of GPVI in the lysate, at time points 3, 7, and 20 minutes, respectively (p<0.2).

Conclusions : Preliminary results show that in the presence of agonists, the ectodomain of GPVI is released into the supernatant in a time dependent manner. This release can be inhibited by resveratrol, quercetin, and naltrexone at a high dose. These results provide a potential new therapeutic method to treat the microvascular nature of POAG. Additional studies are required to affirm these findings.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

 

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