June 2020
Volume 61, Issue 7
ARVO Annual Meeting Abstract  |   June 2020
Tissue plasminogen activator (tPA) in outflow facility regulation
Author Affiliations & Notes
  • Arturo Osvaldo Barron Arrambide
    Ophthalmology and Cell Biology, SUNY Downstate Medical Center,
  • Sofya Gindina
    Ophthalmology and Cell Biology, SUNY Downstate Medical Center,
  • Yan Hu
    Ophthalmology and Cell Biology, SUNY Downstate Medical Center,
  • John Danias
    Ophthalmology and Cell Biology, SUNY Downstate Medical Center,
  • Footnotes
    Commercial Relationships   Arturo Barron Arrambide, None; Sofya Gindina, None; Yan Hu, None; John Danias, None
  • Footnotes
    Support  NIH Grant EY025543
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3452. doi:
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      Arturo Osvaldo Barron Arrambide, Sofya Gindina, Yan Hu, John Danias; Tissue plasminogen activator (tPA) in outflow facility regulation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3452.

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

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Purpose : Studies in tPA knock-out (PlatKO) mice have shown outflow facility (OF) reduction that is associated with a decrease in matrix metalloproteinase 9 (Mmp-9) expression in angle ring tissues (Hu et al., 2019). This study aimed to determine whether intraocular administration of tissue plasminogen activator (tPA) rescues OF in PlatKO mice and if matrix metalloproteinase (Mmp) expression is affected.

Methods : 8-12 week old, female PlatKO mice received intravitreal protein injections (2µl, 5µg/µl) of either tPA in the right eye (OD) or bovine serum albumin (BSA), serving as a control, in the left eye (OS). Two days after the injection, the animals were euthanized and OF was measured in enucleated eyes using a constant pressure perfusion system. Angle ring tissues (containing the trabecular meshwork) were dissected and pooled (N=4) for RT-qPCR analysis of Mmp-9 mRNA expression.

Results : There was a 45.9% enhancement in OF (mean±standard deviation µl/min/mmHg) in PlatKO eyes receiving intravitreal tPA treatment (0.00089±0.000268) as compared to the BSA control (0.00061±0.000218) treated eyes (p=0.003324, t-test). Furthermore, Mmp-9 expression was increased by 2.23±0.638-fold in eyes receiving tPA treatment compared to eyes treated with BSA (p=0.000265, t-test).

Conclusions : Intravitreal injection of tPA restores OF in PlatKO mice. Mmp-9 may serve as an intermediary in this physiologic effect of tPA at the level of the trabecular meshwork.

This is a 2020 ARVO Annual Meeting abstract.


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