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T. Yamamoto, M. Kamei, M. Tsujikawa, M. Suzuki, K. Nishida, Y. Tano; Ttriamcinolone Acetonide Reduces Retinal Toxicity of Intravitreal tPA Under Ischemic Conditions. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2541.
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Intravitreal injection of tissue plasminogen activator (tPA) is used to treat several eye conditions including central retinal vein occlusion (CRVO) and submacular hemorrhage. At the last meeting, we reported that retinal toxicity associated with intravitreally injected tPA can be exacerbated by ischemia. Meanwhile, we clinically tried to treat CRVO with an intravitreal injection of a mixture of tPA and triamcinolone acetonide (TA), and obtained more effective results in reducing macular edema and improving visual acuity. We, therefore, speculated that TA may possibly reduce tPA toxicity to the retina and investigated tPA toxicity when simultaneously injected with TA on a CRVO model.
CRVO was induced in pigmented rats with rose Bengal-assisted laser photothrombosis. One hour after CRVO induction, tPA(3µg) or tPA(3µg)+TA(120µg) was intravitreally injected. The same amount of balanced salt solution (BSS) was injected as a sham control. Eyes were enucleated at 12 hours after injection and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining was performed to evaluate retinal cell apoptosis.
Number of apoptotic cellsmean+SDBSS ; 6.3+2.9tPA3µg ; 84.3+33.5tPA3µg+TA120µg ; 53.6+34.0The number of TUNEL-positive cells significantly (P=0.007, 0.001) increased when tPA or tPA+TA was injected when compared with the control. Comparing the number of apoptotic cells between eyes injected with tPA and eyes injected with tPA+TA, apoptosis decreased in those with tPA+TA without significance (p=0.075)
Retinal toxicity associated with intravitreally injected tPA has a tendency to be reduced with simultaneously injected TA. The dosage of tPA, however, should be reduced when used to treat eyes with ischemic conditions such as CRVO, because an excessive dose of intravitreal tPA still causes retinal toxicity even when injected with TA.
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