Neuroprotective effects of oral lamotrigine administration on rabbit retinas after pars plana vitrectomy and silicone oil injection

Purpose: To investigate potential retinal neuroprotective effects of oral lamotrigine in rabbits after pars plana vitrectomy (PPV) and intravitreal silicone oil injection (SOI). Methods: Twelve New Zealand rabbits (weight, 2.0-2.5 kg) underwent PPV with SOI on the right eye. For 30 days postoperatively, 6 rabbits received a daily oral dose of lamotrigine (25 mg/kg), and 6 rabbits received a daily oral dose of water. The animals were killed 30 days after surgery. All retinas were processed histologically, immunostained using glial fibrillary acidic protein (GFAP), and analyzed by fluorescence microscopy. Retina sections from all groups were analyzed by TUNEL for the presence of apoptosis and stained with hematoxylin-eosin for morphologic analysis and retina cell density measurements in each layer using a Zeiss Axiophot microscope and KS 400 software. Results: Retinas from water-operated eyes showed a significant decrease in cell density associated with cell death compared with retinas from water-control eyes; cell density was reduced by 56% in the outer nuclear layer (ONL), 49% in the inner nuclear layer (INL), and 64% in the ganglion cell layer (GCL). Lamotrigine-operated retinas showed a reduction in cell death when compared with water-operated retinas; cell death was reduced by 52% in the ONL, 25% in the INL, and 56% in the GCL. Water-operated retinas showed TUNEL-positive cells and GFAP immunofluorescence throughout Muller cell processes; lamotrigine-operated retinas showed no TUNEL-positive cells and decreased GFAP staining when compared with water-operated retinas. Conclusions: PPV with SOI was associated with apoptosis of retinal cells and activation of glial cells in rabbit eyes. Oral lamotrigine administration provided protection against these effects

Neuroprotective effects of intramuscular ketamine in rabbit retinas after pars plana vitrectomy and silicone oil injection

To investigate potential retinal neuroprotective effects of intramuscular ketamine in rabbits after pars plana vitrectomy (PPV) and intravitreal silicone oil injection (SOI). Twelve New Zealand rabbits (weight, 2.0-2.5 kg) underwent PPV with SOI in the right eye. Postoperatively, six rabbits received a daily intramuscular injection of ketamine for 4 weeks (ketamine-operated eyes), and six rabbits received a daily intramuscular injection of saline (saline-operated eyes). The retina from the left eye of each rabbit served as a control (ketamine-control and saline-control eyes). The animals were euthanized at 4 weeks after surgery. Qualitative and quantitative analyses were performed using the Zeiss Axiophot microscope and KS 400 software. Qualitative analysis using light microscopy demonstrated more extensive edema and cell disorganization in saline-operated retinas than in ketamine-operated, ketamine-control, and saline-control retinas. Quantitatively, the cell densities (cell/mm) in the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL) in saline-operated retinas were significantly (P < 0.05) lower than those in these layers in ketamine-operated, ketamine-control, and saline-control retinas. The cell density in the ONL in saline-operated retinas was 52% lower than that in ketamine-operated retinas, 55% lower than that in ketamine-control retinas, and 56% lower than that in saline-control retinas. The cell density in the INL in saline-operated retinas was 44% lower than that in ketamine-operated retinas, 48% lower than that in ketamine-control retinas, and 49% lower than that in saline-control retinas. The cell density in the GCL in saline-operated retinas was 60% lower than that in ketamine-operated retinas, 64% lower than that in ketamine-control retinas, and 64% lower than that in saline-control retinas. PPV with SOI was associated with retinal cell death and disorganization in rabbit eyes. Intramuscular ketamine administration provided protection against these effects