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Recombinant tissue plasminogen activator injected into the vitreous cavity may penetrate the retinal veins of a porcine model of vascular occlusion
  1. T H Mahmoud1,
  2. Y-W Peng1,
  3. A D Proia1,2,
  4. M Davidson3,
  5. V A Deramo1,
  6. S Fekrat1
  1. 1Departments of Ophthalmology, Duke University Medical Center, Durham, NC, USA
  2. 2Pathology, Duke University Medical Center, Durham, NC, USA
  3. 3Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
  1. Correspondence to: Tamer H Mahmoud MD, PhD, Vitreoretinal Service, Kresge Eye Institute (Wayne State University), Detroit, MI 48201, USA; tmahmoud{at}med.wayne.edu

Abstract

Aim: To determine if recombinant tissue plasminogen activator (rtPA) injected into the vitreous cavity can penetrate the retinal vessels of porcine eyes with or without vascular occlusion.

Methods: Eight eyes (group I) of four pigs underwent clamping of the optic nerve flush with the globe for 90 minutes. One hour after reperfusion, one eye of each pig was injected with 75 μg of rtPA, and the fellow eye was injected with balanced salt solution (BSS). Eyes were processed for immunohistochemistry. Four additional eyes (group II) of two pigs were subjected to the same injections, but without optic nerve clamping.

Results: After reperfusion, the clinical picture was similar to that of a central retinal vein occlusion. Immunoperoxidase staining showed rtPA only in the retinal veins but not the retinal arteries in all eyes injected with rtPA in both groups I and II. Those eyes also showed intense rtPA staining at the level of the internal limiting membrane (ILM). No staining was seen at the level of the ILM or inside the retinal vessels in the BSS injected eyes. Immunofluorescence staining showed intense staining at the level of the ILM, but not inside the retinal vessels in the rtPA-injected eyes.

Conclusions: rtPA may penetrate the retinal veins, but not the arteries of porcine eyes with and without vascular occlusion. The ILM may play a part in preventing rtPA penetration.

  • BSS, balanced salt solution
  • CRVO, central retinal vein occlusion
  • ILM, internal limiting membrane
  • IF, immunofluorescence
  • IP, immunoperoxidase
  • PBS, phosphate buffered saline
  • RPE, retinal pigment epithelial
  • rtPA, recombinant tissue plasminogen activator
  • animal model
  • internal limiting membrane
  • intravitreous injection
  • retinal vein occlusion
  • tissue plasminogen activator
  • BSS, balanced salt solution
  • CRVO, central retinal vein occlusion
  • ILM, internal limiting membrane
  • IF, immunofluorescence
  • IP, immunoperoxidase
  • PBS, phosphate buffered saline
  • RPE, retinal pigment epithelial
  • rtPA, recombinant tissue plasminogen activator
  • animal model
  • internal limiting membrane
  • intravitreous injection
  • retinal vein occlusion
  • tissue plasminogen activator

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Footnotes

  • T H Mahmoud, MD, PhD, is currently affiliated with the Kresge Eye Institute (Wayne State University), Detroit, MichiganV A Deramo, MD, is currently affiliated with the Long Island Vitreoretinal Consultants, Great Neck, New York

  • Funding support: Supported in part by Research to Prevent Blindness through the Duke University Eye Center small grant committee. The funding source has no involvement in the design, results, or interpretation of the data.

  • Competing interests: none.

  • Presented in part as a poster on 8 May 2002 at the Association of Research in Vision and Ophthalmology meeting in Fort Lauderdale, FL, USA.

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