Smith S B, Titelman R, Hamasaki D I
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912-2000, USA.
Exp Eye Res. 1996 Nov;63(5):565-77. doi: 10.1006/exer.1996.0147.
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.
碱性成纤维细胞生长因子（bFGF）已被证明可挽救RCS大鼠中濒死的光感受器细胞，RCS大鼠是一种具有视网膜色素上皮（RPE）遗传缺陷的模型，该缺陷会损害外节吞噬作用。本研究的目的是确定玻璃体腔内注射bFGF是否会对白癜风（C57BL/6-mi(vit)/mi(vit)）小鼠的光感受器细胞死亡产生类似影响。这种突变小鼠在数月内会缓慢丧失光感受器细胞。实验证据表明，缺陷的主要细胞部位是RPE。在本研究中，将添加和不添加肝素的bFGF在PBS中制备，并在2、4、6、8和13周龄的白癜风小鼠玻璃体腔内注射，此时接近光感受器细胞死亡的开始。未注射、注射PBS和注射肝素/PBS的小鼠作为对照。在处死一组小鼠之前进行暗视视网膜电图（ERG）检查。注射后4、6或10周处死小鼠，对眼睛进行组织学处理并分析。无论注射时间或注射后的持续时间如何，注射bFGF/PBS的小鼠中b波的振幅均显著小于注射PBS和未注射的眼睛。组织学检查显示，注射bFGF、注射赋形剂或未注射的小鼠之间，光感受器细胞的行数没有显著差异。尽管在注射bFGF/肝素/PBS的4周龄突变小鼠中观察到外节与RPE的附着略有改善，但在注射肝素/PBS的突变小鼠中也获得了类似结果。在未添加肝素注射bFGF的小鼠中，视网膜脱离严重，观察到神经视网膜的严重破坏。注射bFGF的小鼠视网膜下间隙中的巨噬细胞和光感受器细胞明显更多。似乎在所给予的剂量和时间下，bFGF在白癜风小鼠中并不能改善视网膜的电生理功能，也不能延缓视网膜的退化，而在RCS大鼠中则可以。
