Effects of basic fibroblast growth factor on the retinal degeneration of the mi(vit)/mi(vit) (vitiligo) mouse: a morphologic and electrophysiologic study

Abstract

Basic fibroblast growth factor (bFGF) has been shown to rescue dying photoreceptor cells in the RCS rat, a model with a genetic defect of the RPE that impairs outer segment phagocytosis. The purpose of the present study was to determine whether intravitreal injection of bFGF would have a similar effect on photoreceptor cell death in the vitiligo (C57BL/6-mi(vit)/mi(vit)) mouse. This mutant mouse loses photoreceptor cells slowly over many months. Experimental evidence suggests that the primary cellular site of the defect is the RPE. In the present study, bFGF was prepared with and without heparin in PBS and injected intravitreally into vitiligo mice at ages 2, 4, 6, 8 and 13 weeks, surrounding the onset of photoreceptor cell death. Non-injected, PBS-injected and heparin/PBS injected mice served as controls. Scotopic ERG's were performed on one group of mice prior to killing. Mice were killed 4, 6 or 10 weeks following the injection and the eyes were processed for histology and analysed. The amplitude of the b-wave was significantly smaller in mice injected with bFGF/PBS than in PBS-injected and non-injected eyes regardless of the time of injection or duration following injection. Histological examination revealed that the number of rows of photoreceptor cells did not differ significantly between bFGF-injected, vehicle- or non-injected mice. Although slight improvement in the attachment of outer segments to RPE was observed in 4 week mutants injected with bFGF/heparin/PBS, a similar result was obtained in heparin/PBS injected mutants. In mice injected with bFGF without heparin, detachment was severe and gross disruption of neural retina was observed. There were significantly more macrophages and photoreceptor cells in the subretinal space in bFGF injected mice. It appears that at the dosages and times administered, bFGF does not improve the electrophysiological functioning of the retina nor retard the degeneration of the retina in the vitiligo mouse as it does in the RCS rat.