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Ruta Maciulaitiene, Symantas Ragauskas, Giedre Pakuliene, Simon Kaja, Ingrida Januleviciene, Giedrius Kalesnykas; Assessment of the effects of systemically administered levetiracetam in an ocular model for neuroprotection.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2571. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the possible neuroprotective properties of systemically administered levetiracetam in the mouse optic nerve crush (ONC) model.
Unilateral ONC was performed on 21 adult (3-month old) male C57Bl/6J mice. Mice were divided into different treatment groups: 1) levetiracetam (UCB Pharma) at a dose of 80 mg/kg loading dose and 40 mg/kg (n=5) daily for a period of 7 days; 2) levetiracetam at a dose of 120 mg/kg loading dose and 80 mg/kg daily afterwards (n=5); 3) vehicle (n=11). All treatments were administered intraperitoneally. Retinal thickness was assessed in vivo using spectral domain optical coherence tomography at baseline and after 7 days. At the end of the follow-up period the animals were transcardially perfused and retinal wholemounts with optic nerves collected. The total number of NeuN positive cells was assessed using stereological quantification. Optic nerves were graded qualitatively and scorred according to no, mild, moderate or severe structural damage as assessed from semi-thin optic nerve cross-sections.
We observed 27.3% decrease in NeuN immonoreactive RGCs in the vehicle group (p<0.01). Levetiracetam exhibited a dose-dependent protection of NeuN-immunoreactive RGCs compared to the contralateral control eye (21.4 ± 2.6% in low dose group and 9.5 ± 5.8% in the high-dose group), corresponding to a 21 ± 4% and 65 ± 1% improvement in cell count, respectively (n=5-11, ANOVA, p<0.05). The higher levetiracetam dose showed a lower number of RGCs in the contralateral control eye, although this difference did not reach statistical significance. Mean retinal thickness was significantly decreased at the end of the 7-day follow-up in all treatment groups as compared to baseline. However, no statistically significant differences were observed between different treatment groups (ANOVA, p>0.05).
Systemic administration of levetiracetam showed neuroprotective effects represented by RGCs survival rate. Additional experiments are needed to evaluate potential dose-dependent confounding effects of the higher levetiracetam dose.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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