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Alejandra Daruich, Marianne Berdugo, Kimberley Delaunay, Marie-Christine Naud, Francine F Behar-Cohen; Analysis of retinal toxicity of recombinant tissue plasminogen activator. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4897.
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© ARVO (1962-2015); The Authors (2016-present)
Intravitreal recombinant tissue plasminogen activator (rtPA) has been proposed for the treatement of submacular hemorrhage in patients with age-related macular degeneration. Moreover, it has been reported that tPA can increase neuronal death after cerebral ischemia by interacting with N-methyl-D-aspartate (NMDA) receptor. We therefore investigated the retinal toxicity of rtPA in healthy rats and in a model of NMDA-induced excitotoxicity.
rtPA was injected in the vitreous cavity in doses of 2.16 µg/5µL, 0.54 µg/5µL and 0.27 µg/5µL. Control eyes received an equal volume of saline solution. Apoptotic retinal ganglion cell were counted ex vivo and electroretinography was performed both at 24 hours and 7 days. We also quantified retinal ganglion cells in two different groups of treatment: NMDA + vehicle and NMDA + tPA 0.27 µg/5µL.
The number of apoptotic cells at 24 hours was significantly (p=0,0250) higher in the group treated by 2.16 µg of rtPA than in the control group. There was no significant difference between the groups treated by 0.54 or 0.27 µg of rtPA and the control group. At 7 days, apoptosis of ganglion cells did not increase in any group. Electroretinogram was not modified either at 24 hours or 7 days. Ganglion cell count in the NMDA + tPA group was similar to the NMDA + vehicle group (p= 0.5887).
0.27 µg of intravitreal rtPA (a dose equivalent to that used clinically) is not toxic for a healthy rat retina. In a model of excitotoxicity, tPA does not enhance NMDA excitotoxicity.
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