June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Penetration of Intravitreal Injected Tissue Plasminogen Activator to the Retina - Rats Model Study
Author Affiliations & Notes
  • Kfir Tal
    Department of Ophthalmology, Rabin Medical Center ,Beilinson Campus Petach Tikva 49101, Israel, Petach Tikva, Israel
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Assaf Dotan
    Department of Ophthalmology, Rabin Medical Center ,Beilinson Campus Petach Tikva 49101, Israel, Petach Tikva, Israel
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Yael Nisgav
    Laboratory of Eye Research, Felsenstein Medical Research Center, Petah Tikva, Israel
  • Mor Dachbash
    Laboratory of Eye Research, Felsenstein Medical Research Center, Petah Tikva, Israel
  • Rita Ehrlich
    Department of Ophthalmology, Rabin Medical Center ,Beilinson Campus Petach Tikva 49101, Israel, Petach Tikva, Israel
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Dov Weinberger
    Department of Ophthalmology, Rabin Medical Center ,Beilinson Campus Petach Tikva 49101, Israel, Petach Tikva, Israel
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  • Tami Livnat
    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Laboratory of Eye Research, Felsenstein Medical Research Center, Petah Tikva, Israel
  • Footnotes
    Commercial Relationships Kfir Tal, None; Assaf Dotan, None; Yael Nisgav, None; Mor Dachbash, None; Rita Ehrlich, None; Dov Weinberger, None; Tami Livnat, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1211. doi:
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      Kfir Tal, Assaf Dotan, Yael Nisgav, Mor Dachbash, Rita Ehrlich, Dov Weinberger, Tami Livnat; Penetration of Intravitreal Injected Tissue Plasminogen Activator to the Retina - Rats Model Study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1211.

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

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Abstract
 
Purpose
 

Tissue plasminogen activator (tPA) is a thrombolytic agent which has the ability to degrade and dissolve fibrin clot. Although the efficacy of intravitreal tPA injections has been shown in clinical practice, the ability of intravitreal Injected tPA to diffuse from the vitreous through the retina and into the subretinal space has been questioned in an experimental models, as tPA conjugated to fluorescein, failed to penetrate the retina. We investigate whether an unconjugated tPA injected into the vitreous could penetrate the neural retina and enter the subretinal space, in a rat model.

 
Methods
 

24 rats eyes were used in the study.14 right eyes were injected with intravitreal tPA (0.75 μg/3 μl), 10 right eyes were injected with intravitreal saline, and served as controls. 3, 24, and 48 hours after tPA injection, animals were euthanized and eyes were taken for cryosections and immunohfluorescence staining. Goat anti tPA, followed by alexafluor 568 donkey anti goat (invitrogene) were used for tPA detection.

 
Results
 

TPA staining was detected in deep retinal layers in all eyes injected with intravitreal tPA. A deeper and more intense staining of tPA was seen after 3 and 24 hours, compared to a decreased staining 48 hours from injection. No staining of tPA was detected in the retina in the eyes injected with saline.

 
Conclusions
 

We demonstrated that an unconjugated tPA at a dose of (0.75 μg / 3 μl) injected into the vitreous penetrates the retina of rats. We speculate that former rabbit model studies that failed to show penetration of tPA to the retina may be explained by the use of conjugated tPA that doesn’t penetrate the retina.  

 
Lack of immunohfluorescence staining in the retina of the eye 3 hours after injected with intravitreal Saline. TPA staining seen here is of vitreous alone. Blue indicate staining of 300 nM 4,6-diamidino-2-phenylidole (Sigma).
 
Lack of immunohfluorescence staining in the retina of the eye 3 hours after injected with intravitreal Saline. TPA staining seen here is of vitreous alone. Blue indicate staining of 300 nM 4,6-diamidino-2-phenylidole (Sigma).
 
 
Goat anti tPA, followed by alexafluor 568 donkey anti goat (invitrogene) were used for tPA detection. TPA staining was detected in deep retinal layers in all eyes injected with 0.75 μg/3 μl intravitreal tPA. Here 24 hours after injection.
 
Goat anti tPA, followed by alexafluor 568 donkey anti goat (invitrogene) were used for tPA detection. TPA staining was detected in deep retinal layers in all eyes injected with 0.75 μg/3 μl intravitreal tPA. Here 24 hours after injection.

 
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