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TH Mahmoud, Y-W Peng, A Proia, M Davidson, VA Deramo, S Fekrat; Intravitreal Tissue Plasminogen Activator Penetrates the Retinal Vessels in a Porcine Model of Vascular Occlusion . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3533.
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Purpose: To test if tPA injected into the vitreous cavity can be detected in the retinal vessels in occlusion and non-occlusion states in a porcine model of vascular occlusion. Methods: Eight eyes (group I) of four 10-week, 15 kg, Yorkshire Cross pigs underwent clamping of the optic nerve flush with the globe, to include the ciliary vessels from which originates the central retinal arcade at the optic nerve head. The clamp was released after 90 minutes. One hour after reperfusion, one eye of each pig (n = 4) was injected with 75 µg (0.075ml) of recombinant tPA (0.1 mg/0.1 ml), and the fellow eye (n = 4) was injected with the same volume of balanced salt solution (BSS). Eyes were enucleated 2 hours after injections while animals remained under general anesthesia, processed by snap freezing in OCT embedding medium, and prepared for immunohistochemistry using a monoclonal anti-tPA antibody and an avidin-biotin-conjugate detection method. Four additional eyes of 2 pigs (group II) were subjected to the same injections (one eye injected with tPA, n = 2, and the fellow eye injected with BSS, n = 2), but without optic nerve clamping. Results: At one minute after occlusion, the arteries became attenuated followed by segmentation of the veins. After reperfusion, we observed immediate dilation and tortuosity of the veins, followed by disc edema. Dot-blot, flame-shaped, and preretinal hemorrhages resembling central retinal vein occlusion developed within 2 minutes. Histopathology of occluded eyes revealed intraretinal edema and hemorrhages at different levels of the retina. Injected intravitreal tPA was detected in retinal vessels in all eyes in both group I and group II. No labeling was detected in the retinal vessels of the eyes injected with BSS in either group. Conclusion: Injection of tPA into the vitreous cavity can penetrate the retinal vessels of pigs. Vascular occlusion or breakdown of the blood retinal barrier does not seem to play a role in the ability of intravitreal tPA to enter the retinal vessels.
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