Purchase this article with an account.
T. Yamamoto, M. Kamei, P. Kunavisarut, M. Suzuki, Y. Tano; Retinal Toxicity of Intravitreal tPA Increases Under Ischemic Conditions . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1488.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Intravitreal injection of tissue plasminogen activator (tPA) has been reported to treat several eye conditions including intraocular fibrin formation, central retinal vein occlusion (CRVO) and submacular hemorrhage, although an excessive amount of intravitreal tPA preparation is toxic to the retina. Toxicity will increase to the retina with CRVO because tPA toxicity to neural tissues increases under ischemic conditions. We, therefore, investigated tPA toxicity to the retina on a CRVO model.
CRVO was induced in pigmented rats with rose bengal assisted laser photothrombosis. Immediately after intravenous rose bengal injection, a laser irradiated major retinal veins adjacent to the optic nerve head. One hour after CRVO induction, (3µl of BSS or tPA(0.075, 0.75 or 3µg) was intravitreally injected. As non–ischemic controls, BSS or tPA (0.75 or 3µg) was injected in untreated eyes. All eyes were enucleated at 12 hours following injection and cryosections were made after fixation. TUNEL staining was performed to evaluate apoptosis of retinal cells. The number of positive cells were counted in three fields under a microscope.
Apoptotic cells increased when 3µg of tPA was injected to non–CRVO eyes, but without statistical significance. The number of positive cells increased in a dose–dependent manner and significantly increased when 3µg of tPA was injected into CRVO eyes. When comparing the number of apoptotic cells between non–CRVO and CRVO eyes with the same treatment, ischemia induced an increase of apoptosis and there was a significant difference between eyes injected with 3µg tPA.
Retinal toxicity of intravitreally injected tPA can increase in a dose dependent manner and with ischemic conditions. These results suggest that the dose of tPA should be reduced when commercially available tPA is applied intravitreally to eyes with ischemic conditions such as CRVO.
This PDF is available to Subscribers Only