Kosaras B, Sidman R L
New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772-9102, USA.
Exp Eye Res. 1996 Aug;63(2):151-8. doi: 10.1006/exer.1996.0103.
The vitiligo mutant mouse has a disorder affecting the interaction of retinal pigment epithelium (RPE) and photoreceptor cells of the neural retina. Among the phenotypic features are patches of hyper- and hypopigmentation in the embryonic RPE, increased RPE cell production neonatally, and a later onset of progressive photoreceptor cell degeneration that continues for more than one year until all photoreceptor cells are gone. Failure of RPE microvilli to intertwine with rod outer segments (ROS) at any age, the accumulation of ROS membranous fragments in the subretinal space, and a relatively early retinal separation from the RPE suggested analysis of whether RPE phagocytosis might be impaired. Post-natal day 23 (P23) and P36 mutant and congenic control wild-type mice were kept in darkness overnight and eyes were examined by light and transmission electron microscopy 0.5 hr before, 1.5 hr after and 10.5 hr after lights turned on at 0700 hr. At these ages ROS have not yet degenerated, though they are shorter than normal and somewhat misoriented. The number of phagosomes per RPE cell was markedly reduced in mutants compared to controls at both ages and all time points. Nonetheless, the highest counts were obtained 1.5 hr after the lights turned on in mutant and control specimens. In the mutant eyes, the proportion of phagosomes in the microvillous zone of the RPE cells was consistently lower than in any other cellular compartment. Phagosome distribution in the apical and basal zones of the RPE cell cytoplasm was within normal limits. Macrophage-like cells become numerous in the subretinal space at older ages, but were already present at P23 and P36, and contained phagosomes in their cytoplasm. The hypothesis is proposed that binding of ROS to RPE cells might be defective in vitiligo mice, in contrast to the rdy rat, where the work of others indicates that binding is normal and the subsequent ingestion of phagosomes is impaired.
白癜风突变小鼠患有一种影响视网膜色素上皮（RPE）与神经视网膜光感受器细胞相互作用的疾病。其表型特征包括胚胎期RPE中色素沉着过多和过少的斑块、新生期RPE细胞产生增加，以及后期逐渐发生的光感受器细胞变性，这种变性会持续一年多，直到所有光感受器细胞消失。在任何年龄，RPE微绒毛都无法与视杆外段（ROS）交织，视网膜下间隙中ROS膜碎片积累，以及视网膜与RPE相对较早分离，这提示需要分析RPE吞噬作用是否受损。将出生后第23天（P23）和P36的突变小鼠及同基因对照野生型小鼠在黑暗中饲养过夜，于早上7点开灯前0.5小时、开灯后1.5小时和10.5小时通过光学显微镜和透射电子显微镜检查眼睛。在这些年龄段，ROS尚未退化，尽管它们比正常的短且方向有些异常。与对照组相比，在两个年龄和所有时间点，突变体中每个RPE细胞的吞噬体数量均显著减少。尽管如此，在突变体和对照样本中，开灯后1.5小时时吞噬体数量最多。在突变体眼中，RPE细胞微绒毛区吞噬体的比例始终低于任何其他细胞区室。吞噬体在RPE细胞质顶区和基区的分布在正常范围内。在老年时，视网膜下间隙中巨噬细胞样细胞数量增多，但在P23和P36时就已存在，其细胞质中含有吞噬体。有人提出假说，与rdy大鼠相反，白癜风小鼠中ROS与RPE细胞的结合可能存在缺陷，在rdy大鼠中，其他人的研究表明结合正常，但随后吞噬体的摄取受损。
