PHAGOSOME NUMBER AND DISTRIBUTION IN RETINAL-PIGMENT EPITHELIAL-CELLSOF VITILIGO MUTANT MICE

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 hypop igmentation in the embryonic RPE, increased RPE cell production neonat ally, and a later onset of progressive photoreceptor cell degeneration that continues for more than one year until all photoreceptor cells a re gone. Failure of RPE microvilli to intertwine with rod outer segmen ts (ROS) at any age, the accumulation of ROS membranous fragments in t he subretinal space, and a relatively early retinal separation from th e RPE suggested analysis of whether RPE phagocytosis might be impaired . Post-natal day 23 (P23) and P36 mutant and congenic control wild-typ e 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 miso riented. The number of phagosomes per RPE cell was markedly reduced in mutants compared to controls at both ages and all time points. Noneth eless, the highest counts were obtained 1.5 hr after the lights turned on in mutant and control specimens. In the mutant eyes, the proportio n of phagosomes in the microvillous zone of the RPE cells was consiste ntly lower than in any other cellular compartment. Phagosome distribut ion in the apical and basal zones of the RPE cell cytoplasm was within normal limits. Macrophage-like cells become numerous in the subretina l space at older ages, but were already present at P23 and P36, and co ntained phagosomes in their cytoplasm. The hypothesis is proposed that binding of ROS to RPE cells might be defective in vitiligo mice, in c ontrast to the rdy rat, where the work of others indicates that bindin g is normal and the subsequent ingestion of phagosomes is impaired. (C ) 1996 Academic Press Limited