Abstract
Abstract: :
Purpose: To study the retinal function and histopathology in rabbits treated with vigabatrin. Methods: Five rabbits were treated with a daily dose of vigabatrin during 1-8 months. Two rabbits receiving water were controls. Full-field electroretinograms (ERG) were performed every two weeks using a Burian-Allen bipolar contact lens. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina (peripheral and central retina) was studied. Blood samples were analyzed every two weeks for determination of vigabatrin serum concentration.10 untreated rabbits were repeatedly examined with ERG for assessment of normal values. Results: The full-field ERG demonstrated normal rod function and reduced cone function in two of five treated rabbits, compared to 10 controls. Immunohistochemical studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery, in all five treated rabbits. The treated rabbits demonstrated a weaker GAD staining of the IPL and less positive amacrine cells, compared to the two controls that were fed with water. In three of five treated rabbits the Muller cells were short, stubby and broken, with swollen endfeet. In all rabbits treated with vigabatrin the serum analyses demonstrated elevated drug concentration. Conclusion: Vigabatrin orally administrated to rabbits may cause a reduced cone b-wave amplitude in the full-field ERG, as previously described in humans treated with vigabatrin. This study demonstrates changes in retinal histopathology in rabbit caused by vigabatrin, which has previously not been reported. Vigabatrin may damage or influence, at least one cell type in the rabbit retina.
Keywords: electrophysiology: non-clinical • drug toxicity/drug effects • retinal glia