Neuroprotective effects of oral lamotrigine administration on rabbit retinas after pars plana vitrectomy and silicone oil injection.
OBJECTIVE
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 Müller 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.
Guizzo
Renato
R
Department of Biology, Faculty of Philosophy, Sciences and Literature, University of São Paulo, São Paulo, Brazil.
Paques
Mila W
MW
Anhezini
Lucas
L
Simon
Cláudio R
CR
Scott
Ingrid U
IU
Jorge
Rodrigo
R
Santos
Wagner F
WF
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007267:Injections; D000077213:Lamotrigine; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012827:Silicone Oils / Q000008:administration & dosage*; D014227:Triazines / Q000008:administration & dosage*; D014821:Vitrectomy
D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D012827:Silicone Oils; D014227:Triazines; D000077213:Lamotrigine