Purpose. To describe the abnormal phenotype in retinal pigment epithel
ium (RPE) and neural retina of vitiligo mutant mice from embryonic sta
ges to old age. Methods. Eyes of wild-type controls and congenic vitil
igo mutants were examined by light and electron microscopy from embryo
nic day (E) 12 to 2 years of age. The amount and distribution of pigme
nt in the RPE was studied in wholemounts. Results. Earliest phenotypic
expression of mi(vit) is seen in the RPE, which is abnormally multila
yered dorsally at E12 to E13, and contains both hyperpigmented and hyp
opigmented patches. Postnatally, most RPE cells have abnormally short,
compact, apical microvilli not containing melanosomes and not interdi
gitating with rod outer segments (ROS). Rod outer segments begin to de
generate relatively late, at approximately postnatal day (P) 30, and f
ragments accumulate in the subretinal space; photoreceptor nuclei decr
ease in number progressively from approximately P60 to P500. Retinal d
etachment, more prominent than in most other retinal degenerations, be
gins as ROS break up. Additional unusual events are the appearance of
macrophage-like cells in the subretinal space by P21 to P60 and extens
ive shedding of photoreceptor nuclei across the external limiting memb
rane and into the subretinal space from approximately P180 to P500. Ph
otoreceptor cell degeneration follows a radial gradient, more severe c
entrally, and is more advanced superiorly than inferiorly. By 2 years,
almost all rod and cone cells are gone, and the residual neural retin
a is invaded by heavily pigmented cells. Conclusions. The initial ocul
ar target of the mi(vit) gene is the RPE, which is abnormal for many w
eeks before photoreceptor cells differentiate and become demonstrably
affected. The authors hypothesize that the slowly progressive photorec
eptor cell degeneration is secondary to abnormal function of the RPE.
This mutation serves to refocus attention on critical influences of th
e RPE on function and maintenance of photoreceptor cells.