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Effects of basic fibroblast growth factor on the retinal degeneration of the mi(vit)/mi(vit) (vitiligo) mouse: a
S B Smith1, R Titelman, D I Hamasaki
1Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912-2000, USA.
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.
Insights
Basic fibroblast growth factor (bFGF) did not protect photoreceptor cells in vitiligo mice. Unlike in RCS rats, bFGF injections worsened retinal degeneration and did not improve electrophysiological function in this model.
Area of Science:
- Ophthalmology
- Retinal Degeneration Research
- Cell Biology
Background:
- Photoreceptor cell death is a hallmark of several retinal diseases.
- Basic fibroblast growth factor (bFGF) has shown neuroprotective effects in some models of retinal degeneration, notably the RCS rat.
- The vitiligo mouse model exhibits slow photoreceptor cell loss due to a defect in the retinal pigment epithelium (RPE).
Purpose of the Study:
- To investigate the efficacy of intravitreal bFGF injections in preventing photoreceptor cell death in the vitiligo mouse model.
- To assess the impact of bFGF on retinal electrophysiology and histology in vitiligo mice.
Main Methods:
- Vitiligo mice received intravitreal injections of bFGF (with or without heparin) or vehicle at various ages.
- Scotopic electroretinograms (ERGs) were recorded.
- Eyes were analyzed histologically at different time points post-injection.
Main Results:
- bFGF injections, particularly without heparin, led to increased photoreceptor cell death and subretinal space infiltration by macrophages.
- ERG b-wave amplitudes were significantly reduced in bFGF-injected eyes compared to controls.
- Histology showed no significant difference in photoreceptor cell counts, though heparin co-administration showed minor improvements in outer segment attachment.
Conclusions:
- Intravitreal bFGF does not appear to be neuroprotective in the vitiligo mouse model of retinal degeneration.
- bFGF administration, especially without heparin, may exacerbate retinal damage in this model.
- The therapeutic effect of bFGF observed in RCS rats is not replicated in the vitiligo mouse model, suggesting model-specific responses.